Splenic lymphoid cells from rats with adjuvant induced polyarthritis show a diminished response to the T-cell mitogens Con A and PHA. This report describes the in vitro effects of various antirheumatic agents on the mitogen induced proliferative response of normal (NSC) and arthritic (ASC) rat spleen cells. Indomethacin enhanced only the arthritic responses. Other PG synthesis inhibitors such as ibuprofen and naproxen enhanced the arthritic as well as the normal spleen cell proliferative responses. Gold sodium thiomalate augmented arthritic but not normal blastogenesis. Penicillamine significantly enhanced only the Con A response of arthritic cells at 10(7)M. Levamisole produced a significant increase in the PHA response of arthritic cells and the Con A NSC response. Chloroquine diphosphate enhanced the Con A response of normal cells at 10(-5)M and 10(-6)M; both chloroquine and tilorone suppressed blastogenesis of arthritic spleen cells at 10(-4)M and 10(-5)M. When classifying antirheumatic agents as stimulator or suppressors of immune function, one must account for their effects on arthritic as well as normal lymphoid cells at the predicted pharmacologic plasma levels.