The hemolytic plaque forming cell assay (PFC), a measure of ability to produce specific antibodies following challenge with antigen, is a powerful predictor of immunosuppression in chemical-exposed rodents. The efficacy of this assay for predicting humoral immunosuppression in non-rodent species remains unknown. In the present report, tilapia (Oreochromis niloticus) were exposed to 9 chemical agents known to inhibit antibody production in mice (benzo[a]pyrene, 7,12-dimethylbenzanthracene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, dimethyl nitrosamine, cadmium chloride, azathioprine, hexachlorocyclohexane, T2 mycotoxin and toluene) and 5 chemical agents which do not inhibit this response (oxymethalone, acetonitrile, diethylstilbesterol, t-butylhydroquinone and formaldehyde). Eight of 9 agents which inhibit antibody production in rodents caused decreased PFC responses in fish. All 5 compounds with negative humoral effects in rodents were also negative in fish. Thus, 13/14 chemical agents tested gave similar results in tilapia as reported in rodents, suggesting a comparable pattern of humoral immunosuppression in chemical-exposed tilapia to that seen in laboratory rodent models.