Four goats, which had been previously bitten on two different occasions by Glossina morsitans centralis infected with Trypanosoma congolense and subsequently treated on each occasion with the trypanocidal drug diminazene aceturate were each fed upon by six uninfected tsetse. Hypersensitivity reactions developed in the skin of two of the goats within 1 hr after the bite, and reached a maximum intensity over the next 24 hr. In order to determine whether hypersensitive skin reactions could be induced by tsetse saliva alone, six different goats were bitten by uninfected tsetse up to eight times. Only a few small nodular skin reactions were noticed. However, following infection and treatment and another sequence of uninfected tsetse bites, hypersensitive skin reactions did occur in two animals, although the reactions were not as severe as anticipated. The hypersensitivity reactions usually precede but sometimes overlap the chancre reaction elicited by metacyclic trypanosomes transmitted by tsetse.