Smallpox is caused by the variola virus. When smallpox was common, it had two main forms: variola major and variola minor. Both forms caused similar skin rashes, but the minor form was much less deadly. Variola major killed about 3 in 10 people infected with it.

After a person is exposed to or comes in contact with the smallpox virus, there is an incubation period of about 10 to 14 days. During this time it causes no symptoms. and the person is not infectious. Once the first sores appear in the person's mouth and throat (early rash stage) they are considered contagious. Sometimes people can be contagious when they have a fever and before the rash develops. But the disease is the most contagious during the early rash and scab periods. The person can spread the virus through direct contact and prolonged face-to-face contact, particularly through coughing. Fluids from the blisters of a person with smallpox are infectious. It is not spread by insects or animals. The person is infectious until the last scab falls off.

One confirmed case of smallpox would be considered a public health emergency.

After the incubation period, the first symptoms of smallpox show up. They are a lot like flu symptoms: fever of 101°F (38.3°C) to 104°F (40°C), headache, back pain, body aches, malaise, and sometimes vomiting. These first symptoms are called the prodrome phase. They last 2 to 4 days. The person is sometimes contagious. Two to 3 days after these symptoms begin, a rash appears, first on the tongue and in the mouth. The rash sores break open and spread the virus in the mouth and throat. The person is most contagious at this time. A rash also breaks out on the skin, beginning on the face. This spreads to the arms and legs, and then to the hands and feet. Within 24 hours, the rash has spread to all parts of the body. The rash then turns into raised bumps (pustules) that fill with fluid and often have a depression in the middle resembling a bellybutton. This is a “hallmark” sign of smallpox. A person is still contagious during this time. These bumps break open and release the virus. Then a crust forms. About 2 weeks after symptoms begin, the bumps form scabs. These scabs also contain the virus. A person with smallpox is contagious until all the scabs have fallen off. When the scabs fall off, scars remain on the skin.

Chickenpox sores (lesions) don't spread over the entire body. They are more likely to be on the trunk than on the face, arms, and legs. A person with chickenpox is usually much less "sick."

When smallpox was common, most people who had it came away with deeply pitted scars on the face and other areas of the body. Before smallpox was done away with, many cases of blindness were caused by the disease.

Currently, no treatment is available to cure smallpox, but the disease can be prevented with the smallpox vaccine. Medicine can also be given to help ease symptoms and treat any bacterial infections that may occur. Smallpox infection with variola major is fatal in up to 30% of those who get it. Research is ongoing to find a medicine that can be used to treat smallpox.

Isolation is important to keep the virus from spreading. All people who have been in contact with the infected person should be vaccinated. Anyone involved in treating the infected person also should be vaccinated.

Because smallpox does not now occur anywhere in the world, there's no longer a national vaccine program for this disease. The last routine vaccines for smallpox in this country were given in 1972. Currently, only certain healthcare workers, emergency response personnel, and military personnel have been given the vaccine. The vaccine usually prevents smallpox infection for at least 10 years. If an outbreak of smallpox does occur, people who are in contact with those infected with the virus can be vaccinated. The vaccine, if given within 4 days after exposure and before the rash appears, can prevent smallpox infection. The vaccine is a live virus related to smallpox. It does not contain smallpox and cannot cause it. In people who were vaccinated as children, any later infection with the virus might cause only a mild form of the disease, health experts say.

The healthcare provider uses a 2-pronged needle that is dipped into the vaccine. The healthcare provider pricks the skin of the upper arm with the needle several times. The pricking causes a sore spot on the arm. If the vaccine is successful, a red, itchy bump appears where the vaccine was given. After a few days, the bump fills with fluid and begins to drain. A scab then forms. After 3 weeks, it falls off, leaving a small scar.