The immunotoxic potential of NiCl2 was evaluated in Fischer 344 rats following a single intramuscular injection at doses ranging from 10 to 20 mg/kg. Twenty-four hours following treatment, selected cellular and humoral immune function parameters were examined. Significant (P>0.05) decreases in body weights were observed in rats injected with 15 and 20 mg/kg NiCl2 as were decreased in spleen weights of rats receiving 20 mg/kg. The lymphoproliferative responses of splenocytes to the T cell mitogens concanavalin A (ConA), phytohemagglutinin (PHA) and pokeweed mitogen (PWM) and the B cell mitogen Salmonella typhimurium mitogen (STM) were not significantly different from controls. No significant differences were observed between control and Ni-treated rats in the primary antibody response to sheep red blood cells (SRBC). On the other hand, natural killer (NK) cell activity was significant (P<0.05) suppressed in rats injected with 10, 15, or 20 mg/kg NiCl2. NK cell suppression was observed in both male and female rats and for both allogeneic W/Fu-G1 target cells as well as xenogeneic YAC-1 target cells. Ni-induced suppression of NK activity was transient, with levels returning to control values within three days following treatment. Ni-induced suppression of NK activity was also manifested by an increase in mortality of rats injected with MADB106 tumor cells.