T-cell responses were studied in mice immunized with the Salmonella typhimurium aroA SL3261 live attenuated vaccine strain. T-cell responses in the spleen, both in whole cell populations and in nylon wool non-adherent (T-cell enriched) cells, were studied in vitro as proliferation by incorporation of tritiated thymidine and production of T-cell specific cytokines [IL-2 (interleukin-2)/IL-4]. Stimulating antigens included whole Salmonella lysates and purified lipopolysaccharide (LPS), both untreated and after alkaline hydrolysis to prevent the non-specific mitogenic effect of LPS. Strong proliferative responses were obtained with untreated whole cell extract and LPS, which were decreased by polymyxin B (PB). Alkaline detoxification of the antigens decreased the proliferative response of nylon-wool non-adherent populations to LPS, but greatly increased their response to the Salmonella extract. Surprisingly, PB also reduced proliferation to detoxified LPS. Little or no IL-2/IL-4 production was seen in response to LPS or purified polysaccharide antigens, while there was a strong IL-2/IL-4 response to whole cell lysate, again markedly increasing after alkaline treatment. The results suggest that the T-cell response elicited by immunization with live Salmonella aroA vaccines in mice recognizes antigens other than LPS determinants, and that estimation of T-cell responses to Salmonella antigens by proliferation alone may yield misleading results.