Smallpox is a severe, highly contagious disease caused by the variola virus. It killed roughly 30% of the people it infected in its most common form and left survivors with deep, permanent scars. Thanks to a global vaccination campaign, smallpox became the first human disease ever eradicated. The World Health Assembly officially declared it eliminated on May 8, 1980, and no naturally occurring case has been reported since 1977.
What Causes Smallpox
Smallpox is caused by the variola virus, a member of the poxvirus family, which contains the largest of all known viruses. Under an electron microscope, each viral particle looks like a tiny brick, roughly 400 by 200 nanometers, with a ridged outer surface and a dumbbell-shaped core of tightly compressed genetic material inside. That core carries enough DNA to encode about 200 different proteins, giving the virus a complex toolkit for hijacking human cells and evading the immune system.
Two forms of the virus cause disease in humans. Variola major is the more common and dangerous strain, with a fatality rate of about 30%. Variola minor causes a milder illness and kills roughly 1% of those infected. Both strains spread the same way and produce similar symptoms, but variola major causes more extensive rash, higher fevers, and far more deaths.
How Smallpox Spreads
Smallpox spreads primarily through face-to-face contact. When an infected person talks, coughs, or sneezes, they release large virus-laden droplets of saliva that a nearby person can inhale. This required fairly prolonged, close contact, which is why outbreaks often burned through households and hospitals rather than sweeping through crowds the way influenza does.
The virus can also spread through contaminated materials. Clothing, bedding, or objects that came into contact with the fluid from smallpox sores or dried scabs could carry the virus. In rare cases, it traveled through the air in enclosed buildings.
A person with smallpox becomes contagious as soon as the first sores appear in the mouth and throat, and they remain infectious until the very last scab falls off their body. That contagious window can stretch over three weeks or more.
Symptoms and Timeline
Smallpox unfolds in distinct stages over roughly a month. After exposure, the virus silently multiplies inside the body for 7 to 19 days (10 to 14 on average). During this incubation period, a person looks and feels completely normal.
Prodrome: Days 1 to 4
The illness announces itself suddenly with a high fever, severe headaches, body aches, and sometimes vomiting. Most people are too sick to carry on daily activities. At this point, the disease can look like many other infections, and there is no rash yet to signal what’s coming.
Early Rash: Days 4 to 8
Small red spots appear first on the tongue and inside the mouth. These quickly break open into sores that release large amounts of virus into the mouth and throat. Within about 24 hours of the mouth sores appearing, a skin rash spreads in a distinctive pattern: starting on the face, moving to the arms and legs, then reaching the hands and feet. By the fourth day of rash, the spots fill with a thick, opaque fluid and often develop a characteristic dent in the center.
Pustules and Scabs: Days 8 to 24
The fluid-filled sores become firm, raised pustules that feel like peas under the skin. After about five days in this stage, the pustules begin to crust and form scabs. By the end of the second week of rash, most sores have scabbed over. Then, over a final stretch of about six days, the scabs fall off and leave behind pitted marks on the skin. Three weeks after the rash first appeared, most scabs have separated.
How Smallpox Differs From Chickenpox
Because both diseases produce blistering rashes, they can look similar at first glance. But several key differences set them apart.
- Lesion consistency. Smallpox sores are all at the same stage of development at any given time. If one spot is a blister, they all are. Chickenpox lesions appear in waves, so you’ll see a mix of new spots, blisters, and scabs on the body simultaneously.
- Rash distribution. Smallpox rash starts on the face and extremities and spreads inward toward the trunk. Chickenpox does the opposite, starting on the scalp and trunk and spreading outward. Smallpox sores commonly appear on the palms and soles, which rarely happens with chickenpox.
- Lesion texture. Smallpox pustules are deep-seated, firm, round, and well-defined, with a dimpled center. Chickenpox blisters are superficial and delicate, often described as “dewdrops on a rose petal.”
Long-Term Effects on Survivors
Surviving smallpox did not mean walking away unscathed. The deep-seated pustules destroyed tissue as they healed, leaving many survivors with permanent, pitted scars over large areas of their bodies, especially the face. Some survivors were left blind, a result of the virus attacking the eyes when sores formed on or near the cornea. These disfiguring outcomes were one of the reasons smallpox carried such intense cultural fear for centuries.
How Vaccination Works
Smallpox vaccines don’t use the variola virus itself. Instead, they use a related virus called vaccinia, which belongs to the same genus but causes far milder disease. Exposure to vaccinia trains the immune system to recognize and fight variola if it ever encounters the real thing.
Two main vaccines sit in the U.S. Strategic National Stockpile today. The first, ACAM2000, contains live vaccinia virus that can actually replicate in the body. It’s highly effective, but because the virus is alive and active, it can spread from the vaccination site to close contacts through skin-to-skin contact. The second, JYNNEOS, uses a weakened form of the virus that cannot replicate. This makes it safe for people with compromised immune systems or skin conditions like eczema, who could face serious complications from the live vaccine.
Routine smallpox vaccination stopped after eradication, so most people born after the late 1970s have never been vaccinated. The stockpiled vaccines exist as a safeguard in case the virus were ever deliberately released.
How Smallpox Was Eradicated
Eradication succeeded because smallpox had several biological vulnerabilities. It had no animal host to hide in, so every case existed in a human being who could be found and isolated. The rash was visible and distinctive, making cases hard to miss. And the vaccine worked even when given shortly after exposure, which meant health workers could surround an outbreak by vaccinating everyone in contact with a sick person.
The World Health Organization launched its Intensified Eradication Programme in 1967 and deployed this “ring vaccination” strategy worldwide. The last person to catch smallpox naturally was Ali Maow Maalin, a hospital cook in Somalia who developed symptoms on October 22, 1977. He was initially misdiagnosed with malaria and then chickenpox before eradication staff correctly identified the disease on October 30. He survived, and no further natural cases followed.
Where the Virus Still Exists
Although the disease is gone, the virus itself is not. Samples of variola virus are kept at two WHO-authorized laboratories: the Centers for Disease Control and Prevention in Atlanta, Georgia, and the Russian State Centre for Research on Virology and Biotechnology in Koltsovo, Russia. These stocks are maintained under strict biosecurity for ongoing research, including the development of treatments and improved vaccines. Whether to destroy these remaining samples has been debated for decades, with no final resolution.