The effect that dietary exposure to the naturally-occurring Fusarium graminearum toxins deoxynivalenol (DON) and zearalenone (ZEA) may have on immune function was assessed in the B6C3F1 mouse. Dietary DON depressed the plaque-forming response to sheep red blood cells, the delayed hypersensitivity response to keyhole limpet haemocyanin and the ability to resist Listeria monocytogenes. Listerial resistance was similarly decreased in control mice fed restricted diets comparable to the dietary restriction caused by DON-induced feed refusal, whereas equivalent food restriction did not decrease the plaque or delayed hypersensitivity responses. ZEA ingestion decreased resistance to L. monocytogenes but did not affect splenic plaque-forming or delayed hypersensitivity responses. Resistance to Listeria was reduced to a greater extent by co-administration of DON and ZEA than by DON alone, whereas the ability of DON to inhibit the delayed hypersensitivity response was significantly lessened in the presence of ZEA. While effects on resistance to Listeria and delayed hypersensitivity were detectable in mice ingesting the mycotoxins for 2-3 wk, these effects disappeared upon extension of the feeding period to 8 wk. In contrast, some effect on the plaque-forming response was detectable with both the 2- and the 8-wk period of mycotoxin ingestion. Immunosuppression can thus result from ingestion of F. graminearum-infected agricultural staples, the suppression being attributable to interactions between direct immunotoxic effects of DON and ZEA and nutritional effects associated with DON-induced food refusal.