We are interested in potential interactions between environmental trace metal exposures and immune function. In particular, we have wondered whether dietary exposure to nickel and zinc cations can influence T and B cell proliferation and function. To study this question, we fed SJL female mice supplemental nickel and zinc sulfate from 4-8 weeks of age, and immunized the animals intraperitoneally (i.p.) with keyhole limpet hemocyanin (KLH) at 8 weeks. Eight days later, we measured antibody responses to KLH. Both IgG and IgM antibody responses to KLH were significantly depressed in vivo in the nickel fed animals (p less than 0.005). In vitro antigenic responsiveness to KLH of splenocytes from nickel fed animals was also depressed compared with control and zinc supplemented animals (p less than 0.002). This altered antigenic responsiveness persisted even after cells had been cultured for 5 days in standard media. The zinc supplemented diets did not seem to affect antibody responsiveness and proliferation. The proliferative responses of B cells to the mitogen lipopolysaccharide (LPS) were significantly depressed in Ni fed mice, but were not affected in the zinc fed animals. T cell mitogenic responses to concanavalin A were not affected in the nickel fed animals, and were enhanced in zinc fed animals. We conclude that dietary exposure to certain trace metals may induce persisting alterations in immunity in this animal model.