Wild juvenile cotton rats (Sigmodon hispidus) were used in this study to examine the effects of exposure to cyclophosphamide (CY) or differing levels of benzene on selected measures of cellular immunity following dietary protein restriction. Benzene caused marginal immunotoxicity as indicated by suppressed splenocyte proliferation and total circulating neutrophils. Cyclophosphamide and also crude protein restriction induced severe immune lesions manifested as thymus and spleen atrophy, depressed delayed hypersensitivity response, reduced proliferative capacity of splenocytes, and reduced numbers of total leukocytes, lymphocytes, and splenocytes. Although severe immune modulation resulted from the individual effects of CY exposure and dietary protein restriction, there was little statistically significant toxicant-diet interaction.