Atrazine (ATZ) is used throughout North America to control annual broadleaf weeds and grasses in various crops including; corn, sorghum, and sugar cane. Unfortunately, contamination of surface and ground water has occurred as a result of ATZ's chemical and physical properties, and its widespread use throughout the U.S. Midwest. A study of ATZ's immunomodulatory properties was conducted using female B6C3F1 mice and a panel of immune assays and host resistance models designed to evaluate cell-mediated and antibody-mediated immunity. Mice were administered ATZ by gavage (0, 24, 250, and 500 mg/kg/day) for 14 days then evaluated for immune responsiveness. ATZ treatment significantly increased the number of splenic CD8+ T cells, cytotoxic T cell and mixed leukocyte responses, and dose-dependently reduced host resistance to B16F10 melanoma. Thymus and spleen weights, total spleen cell numbers and fixed macrophage function was also reduced in mice that were exposed to ATZ. These results demonstrate that oral ATZ exposure is sufficient to alter cell-mediated immune function and disease resistance in female B6C3F1 mice.