In mice chronically infected with Trypanosoma cruzi there are antigen-specific suppressor cells which inhibit the development of delayed hypersensitivity (DTH) to T. cruzi antigen but not to an unrelated antigen, keyhole limpet haemocyanin (KLH). This was shown by comparing the 24 hr footpad reactivity, elicited by injection of soluble T. cruzi antigen, of infected mice with that of mice immunized with killed T. cruzi antigen after pretreatment with cyclophosphamide. In the latter, 24 hr footpad swelling represented a DTH reaction in that the cellular infiltrate was predominantly mononuclear and the reactivity could be transferred to normal recipients by lymphoid cells but not by serum. Chronically-infected mice also developed 24 hr footpad swelling but the fact that this was undiminished from an earlier 3 hr reaction and could not be transferred to normal recipients by either local or systemic injection of cells, as well as the histological features, all implied that it represented a prolonged Arthus reaction. The absence or minimal levels of specific DTH detectable in chronic T. cruzi infected mice was accompanied by the presence in their spleens of cells which specifically suppressed the generation of DTH to T. cruzi in normal mice. Suppressor cell activity was radioresistant (10 Gy/1000 rad) and T-cell mediated as defined by significantly decreased and increased suppression following anti-Thy 1.2 serum treatment and nylon wool fractionation, respectively. The ability of chronic T. cruzi mice to develop DTH to an unrelated antigen KLH was unimpaired.