C57BL/6 mice were administered 50 or 200 ppm of Cd as CdCl2 in the drinking water for either 3 to 4 (short term) or 9 to 11 (long term) weeks. In other experimental designs, mice were exposed orally to 300 ppm of Cd or injected with 2.5 mg/kg of Cd ip. The proliferative response to the T cell mitogens Con A and PHA was increased in cultures of spleen cells from orally treated mice in most of the experiments performed. After primary immunization with sheep red blood cells, the number of IgM antibody forming cells per 10(7) spleen cells was also moderately higher in mice exposed to 50 or 200 ppm of Cd for short or long term. In contrast, long-term exposure to 300 ppm of Cd depressed the antibody response to SRBC. Administration of ZnCl2 prevented the enhancement of the PFC response in mice orally administered 50 ppm of Cd. The capacity to suppress the antibody response of spleen cells preincubated with sodium periodate was decreased after short-term oral or ip. Cd administration but was completely or partially recovered after long-term exposure to either 50 or 200 ppm of Cd.