In order to assess the effects of the fungal toxin wortmannin on the immune system, rats and mice were fed wortmannin-containing cultures of Fusarium oxysporum for 1 or 2 weeks. Wortmannin caused significant decreases in thymic weight, thymic lymphocyte numbers, serum IgG and IgM levels, the primary humoral response to T-dependent and T-independent antigens and the proliferative response of spleen cells to pokeweed mitogen. In vitro administration of wortmannin did not produce evidence of cytotoxicity to spleen or thymus cells. The data indicate that wortmannin inhibits immune function in rats and mice and suggest that metabolic modification of the toxin is necessary for toxicity.