Mice were immunized with either poly(Glu, Arg, Ala) or poly(Glu, Lys, Phe) contained in two different adjuvant preparations, alum (A1K(SO4)2) or complete Freund's adjuvant (CFA), and in vitro antigen-driven proliferative responses of lymph node cells were assayed 4-16 days later. After immunization with antigens on alum, endogenous interleukin 1 (IL-1) as well as interleukin 4 (IL-4) production was required for the proliferation of the elicited T cells as inclusion of either polyclonal goat anti-mouse IL-1 alpha or monoclonal anti-mouse IL-4 (11B11) in the cultures inhibited proliferative responses to antigen. In contrast, proliferative responses of cells elicited by antigen in CFA were not inhibited by either anti-IL-1 or anti-IL-4. Monoclonal antimouse CD4 (GK 1.5) inhibited proliferative responses regardless of which adjuvant was used to elicit antigen-reactive cells. These data indicated that phenotypically different subpopulations of CD4+ cells were elicited by the same antigen administered in different adjuvant preparations, Th2-like cells after immunization with polymers on alum and Th1-like cells after immunization with antigens in CFA. An examination of the isotypes of polymer-specific antibodies present in the sera of immunized mice also supported this conclusion.