This study assessed early effects of short-term Cd exposure on T and B cell responsiveness. Spleen cells from mice injected s.c. with a daily dosage of 1 mg, 0.33 mg, or 0.11 mg Cd (as CdCl2) per kg body weight for 5 days were examined for their potential to generate alloreactive T cells in a mixed lymphocyte reaction (MLR) and for mitogen reactivity to concanavalin A (Con A) in vitro. Spleen cells from the same mice were also assayed for the total number of IgM- and IgG-secreting B cells. Whereas alloreactivity was reduced, mitogen response to Con A was not different from controls or was even enhanced. The decrease in allogeneic MLR was dependent on the injected Cd dosage. No difference in susceptibility to Cd-induced effects was observed among the mouse strains tested, i.e. BALB/c, DBA/2, C57BL/6, and C3H/He. Co-cultivation of spleen cells, obtained from Cd-treated mice that exhibited deficient T cell reactivity, with splenic responder cells from untreated mice resulted in dose-dependent suppression of the normal MLR. These results indicate that the harmful effects of Cd on the immune system include the inhibition of antigen-specific T cell responses by the activation of an antigen non-specific suppressor system. In contrast to the suppressed allogeneic MLR, the same spleen cell populations showed augmented numbers of IgM- and IgG-antibody producing cells.