Perfluorooctanesulfonate (PFOS) is a widespread contaminant in the environment, as well as in wildlife and in humans. Toxicity tests in rodents have raised concerns about potential developmental, reproductive, and systemic effects of PFOS. However, there is little information about the effect of PFOS on immune system. In this study, adult male C57BL/6 mice were given by gavage 0, 5, 20 or 40 mg PFOS/kg day(-1) for 7 days. The results showed that PFOS exposure decreased food intake and body weight and increased liver mass and serum corticosterone levels in a dose-dependent manner. Flow cytometry analysis showed that the number of lymphocytic subpopulation cells decreased significantly in 20 or 40 mg PFOS/kg day(-1) group in comparison with normal C57BL/6 mice. Treatment with PFOS also markedly depressed the natural killer (NK) cell activity, lymphocyte proliferation and the plaque-forming cell (PFC) response. These results indicate that PFOS exposure can affect the immunity function in mice.