While the first true vaccine for smallpox was not invented until 1796, the practice of deliberately inoculating people with a mild form of the disease was established decades earlier. The British military likely employed such deliberate infection to spread smallpox among forces of the Continental Army.

The British routinely inoculated their own troops, exposing soldiers to the material from smallpox pustules to induce a mild case of disease and, once they recovered, life-long immunity. But in Boston, and perhaps also Quebec, the British may have forced smallpox on civilians. As they fled the besieged cities these civilians, the British hoped, would carry smallpox to rebel troops.

In Boston the mission seems to have failed; the infected civilians were quarantined and thus kept from Continental soldiers. But in Quebec, smallpox swept through the Continental Army, helping to prompt a retreat.

Using smallpox as a weapon was not unprecedented for the British military; Native Americans were the targets of attack earlier in the century. One infamous and well-documented case occurred in 1763 at Fort Pitt on the Pennsylvania frontier. British Gen. Jeffery Amherst ordered that blankets and handkerchiefs be taken from smallpox patients in the fort's infirmary and given to Delaware Indians at a peace-making parley.