Smallpox (variola) is an infectious disease caused by a DNA virus of the genus orthopox. The smallpox virus is distinct from that of cowpox, a disease of the udders of cows, but infection with cowpox virus ("vaccination," from vaccus, a cow) confers immunity against smallpox without significant illness. Smallpox is spread by droplets from the nose and throat or by dried viral particles on blankets and clothing. After infection, the nonimmune subject is well for an incubation period of about 12 days. The illness usually begins with backache, fever and prostration, followed by a pustular rash affecting chiefly the face and limbs. During the phase of the rash, which lasts a few weeks, the patient is likely to infect from 3 to 5 close contacts. The rash leaves pitted scars or pocks. Complications include pneumonia, blindness, infection of joints or bones. A haemorrhagic form is invariably fatal. In variola major the mortality rate is 30-40%, whereas in variola minor the rate is only 1-2%.

Smallpox may have been prevalent in Asia in ancient times but was first described for certain by Rhazes in the 9th century AD in Asia Minor. The disease was brought to America by Spaniards visiting and conquering Caribbean islands (1507) and Mexico (1519). It was reported first in New France in 1616 near Tadoussac, brought by French settlers to the St Lawrence and Saguenay River regions. Because the Aboriginal peoples were totally devoid of immunity, they were ravaged by smallpox, which quickly spread to tribes in the Maritimes, James Bay and Great Lakes area. Between 1636 and 1640 Jesuit priests introduced smallpox into HURONIA west of Lake Simcoe and south of Georgian Bay. Because priests baptized the sick and dying Aboriginal people, their visits spread the disease, which Aboriginal people perceived as the evil "medicine of the black robes."

Smallpox played a significant role in the struggles of French, British and Americans to dominate the St Lawrence area. The worst epidemic in French Canada occurred between 1755 and 1757 and spread to New England. De Vaudreuil, the French commander, was forced to abandon his invasion of New England. In 1757, Montcalm reported 2500 cases in Québec City, of whom 20% died. British troops besieging Louisbourg and attempting to invade Québec were affected. In 1763, the British used blankets exposed to smallpox as germ warfare in their attempt to subdue the Aboriginal uprising led by PONTIAC. In 1775 during the AMERICAN REVOLUTION American troops besieging Québec City were stricken with smallpox.

Vaccination was introduced into North America in 1798 by the Reverend John Clinch, a classmate of Edward Jenner, who first proved that vaccination prevented smallpox. The widespread use of vaccination, advocated by public-health leaders, met with much resistance by anti-vaccinationists. Although provincial legislation was passed making vaccination of schoolchildren mandatory and empowering municipalities and townships to carry out general vaccination when an epidemic threatened, passive resistance was widespread. In Montréal in 1885 a major outbreak occurred, ultimately resulting in over 3000 deaths. Many French Canadians in Montréal opposed vaccination. The attempts to enforce control measures, plus the announcement in September 1885 that Louis Riel, leader of the North-West Rebellion, had been sentenced to death, resulted in street rioting which could only be suppressed by calling out the militia.

Smallpox smouldered in Canada during the first half of the 20th century. In 1924 in Windsor, Ont, there were 67 cases with 32 deaths, all in unvaccinated persons. The disease was finally eradicated in 1979 by a vigorous vaccination campaign in S America, Africa and Asia carried out by the World Health Organization. Smallpox is the first major disease to have been wiped out by public-health measures.