Effects of itraconazole (ICZ) on the immune responses were studied in ICR mice. Mice were divided into 5 groups (10 mice/group), and ICZ at doses of 10, 20, 40 and 80 mg/kg were orally administered to mice once a day for 21 days. Mice were immunized and challenged with sheep red blood cells (SRBC). The body weight gains and the relative weights of spleen and thymus were dose-dependently increased following ICZ treatment. However, Plaque forming cells (PFC) and hemagglutination (HA) titers to SRBC were significantly suppressed in mice doses at 80 mg/kg ICZ, as compared with those in controls. Delayed-type hypersensitivity (DTH) reaction to SRBC, phagocyte activity and circulating leukocytes also were significantly decreased in mice dosed at 40 and 80 mg/kg ICZ. These studies demonstrate that ICZ treatment results in a marked suppression in both humoral and cell-mediated immune responses to SRBC at concentrations producing embryotoxicity.