The effect of a 14-day treatment with low doses of O,O,S-Trimethyl phosphorothioate (OOS-TMP), an impurity in technical malathion, on the generation of cell-mediated and humoral immune responses was examined in female C57B1/6 mice. At a dose of 0.5 mg/kg/day OOS-TMP, the generation of antibody-secreting cells to sheep red blood cells (SRBC), the production of interleukin 2 (IL-2), and proliferative responses to the mitogens concanavalin A (Con A) and lipopolysaccharide (LPS) were elevated. In contrast, the cytotoxic T-lymphocyte (CTL) response to alloantigen was unchanged. At 5.0 mg/kg/day OOS-TMP, both the CTL and specific antibody response were unchanged, but all other immune parameters examined were elevated. Data from cell separation and reconstitution experiments indicated that both macrophages and B cells were affected by this treatment regime. These data suggest that long-term exposure to low amounts of OOS-TMP may enhance the ability of an animal to generate an immune response.