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The regiment was named after William Pepperell who was made a baronet in 1746 for his exploits in the Siege of Louisbourg the previous year. He was the first American so honored, and given a colonel's commission in the British Army to raise his own regiment.
Two regiments were raised in New England with funds supplied by the British Crown, entering the army list as the 50th (Shirley's) and 51st (Pepperrell's) Regiments of Foot. Both regiments took part in the disastrous British campaign of 1755/56.
Overwintering near Lake Ontario, the 50th and 51st occupied three forts, Oswego, Ontario and George, collectively known as Fort Pepperrell. Surrounded and besieged by a French force under Montcalm, both regiments surrendered after the local commander was killed. A fair number of the prisoners were massacred by the Indian allies of the French before they reached Montreal.