Fumonisins represent a family of toxic, structurally related metabolites produced by fungi that are found in corn worldwide. We investigated the effects of the mycotoxin, fumonisin B(1), on rat splenic macrophage and lymphocyte functions. Pretreatment (24 h) of resident macrophages with fumonisin B(1) (1, 10, and 100 microg/ml) significantly (p<0.01) stimulated nitric oxide production (0.48, 2. 60, and 4.40 nmol nitrite/well, respectively), compared with the response of untreated macrophages (no nitrite detected), after 72 h of culture. Fumonisin B(1) (1 and 10 microg/ml) and IFN-gamma acted in an additive manner to activate nitric oxide production. The response of IFN-gamma (50 U/ml)-activated macrophages (1.68 nmol nitrite/well) was potentiated (3.52, 4.96, and 4.44 nmol nitrite/well) by fumonisin B(1) (1, 10, and 100 microg/ml, respectively). In addition, fumonisin B(1) significantly (p<0.05) potentiated Con A (1.25 to 5 microg/ml) (1.46- to 2.62-fold increases)- and antiTCR, IL-2 or antiTCR+IL-2 (1.72- to 2.60-fold increases)-induced proliferation of splenic cells in the presence of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (NMA). These results show two distinct and separate effects of fumonisin B(1): it induces nitric oxide production by macrophages and it stimulates T cell proliferation.