The effects of fumonisin B 1 (FB 1), a mycotoxin produced by Fusarium vertcillioides, on the immune system are controversial; FB 1 exposure causing immunosuppression in poultry, swine, bovine and rodents species and immunostimulation in rodent species. The current study was conducted to examine the effects of FB 1 on the immune system of BALB/c mice and to determine if there is sex specificity. Female and male mice (five per group) received five daily subcutaneous (s.c.) injections of 2.25 mg/kg/day of FB 1, on the following day tissues were collected for immunological examinations. FB 1 treatment dramatically reduced relative spleen and thymus weights in females, whereas there was no effect on organ weights in males. Exposure to FB 1 reduced splenic cellularity and the basal rate of lymphocyte proliferation in females only. In addition, phytohemagglutinin (PHA-P)-induced T-lymphocyte and LPS-induced B-lymphocyte proliferation were reduced in female mice. Splenocytes from female mice exposed to FB 1 showed a reduced expression of interleukin-2 mRNA. These changes occurred in the absence of alterations in tumor necrosis factor α or interleukin-1β mRNA expression. Phenotypic analysis indicated that FB 1 treatment caused a relative increase in the T-lymphocyte population in the spleen of female mice only. In contrast, FB 1 dramatically reduced the immature CD4 +/CD8 + double positive cell population in the thymus of females. No changes were evident in the thymocyte populations of male mice treated with FB 1. The results of this study indicate that FB 1 is immunosuppressive in mice; the magnitude of FB 1-induced immunosuppression is highly dependent on sex, females being more susceptible than males.