When lipid A nonresponsive C3H/HeJ mice were intubated with SRBC and subsequently orally immunized with TNP-SRBC, higher splenic anti-TNP PFC responses were observed than with similarly treated syngeneic, LPS-responsive C3H/HeN mice. Oral administration of Con A at the time of TNP-SRBC immunization resulted in enhanced immune responses in both mouse strains. Anti-TNP PFC responses, mainly of the IgA class, were higher in the C3H/HeJ strain. High responses correlated with the induction of greater T cell help in gut-associated lymphoid tissue (GALT). Peyer's patches (PP) T cells from C3H/HeJ mice always promoted greater responses in T cell-depleted spleen cultures (B cultures) than were seen with C3H/HeN PP T lymphocytes. Prior treatment of PP T cells with anti-Thy-1 antibody and C abrogated in vitro responses. When Peyer's patch cultures from normal or carrier-primed mice were immunized with TNP-SRBC, no in vitro immune responses occurred in either mouse strain unless the macrophage monokine, Interleukin 1 (Il 1) was added to the culture. C3H/HeJ PP cultures from carrier-primed mice yielded higher responses than C3H/HeN cultures in the presence of II 1. Mesenteric lymph node (MLN) cultures from carrier-primed C3H/HeJ mice exhibited higher in vitro responses to TNP-SRBC than did C3H/HeN MLN cultures. When submitogenic concentrations of Con A were tested with SRBC-primed PP T cells in splenic B cell cultures, those containing C3H/HeJ PP T cells yielded enhanced in vitro responses to TNP-SRBC. These results suggest that oral administration of T-dependent antigens to C3H/HeJ mice results in increased T helper cell induction in GALT and leads to higher IgA responses in this mouse strain.