The effect of cyclosporin A (CsA) on the in vitro induction of sheep red blood cell (SRBC)-specific T cells mediating the delayed-type hypersensitivity (DTH) reaction was studied. CsA (1 microgram/ml) addition to the culture medium totally inhibits the in vitro anti-SRBC humoral response but does not interfere with the generation of anti-SRBC DTH-mediating T (TDTH) cells. The induction of TDTH requires the presence of antigen and their expression is mediated selectively by the antigen used in the culture. The TDTH cells generated are Lyt-1+,2- and their induction occurs with a similar efficiency in CsA-treated and untreated cultures: the frequency of the TDTH cells increases by a factor of 10 to 20 during the 6-day incubation period. Lyt-2+ suppressor cells are also generated in CsA-treated or untreated cultures. Our results suggest that a small fraction of T cells can be driven into the proliferative pathway by antigen even in presence of CsA.