Both cholecystokinin (CCK), a short-term meal-related satiety signal, and the ob protein leptin, a postulated long-term adiposity hormone, are thought to be important signals in the multiple interacting systems that control appetite and adiposity. We hypothesized that these hormones may synergistically interact to suppress feeding. Following IP administration of leptin (two doses of 50 mu g each) and CCK (2, 4, 8, or 16 mu g) total daily caloric intake was significantly reduced by leptin and CCK compared to leptin alone. These results support the hypothesis that CCK and leptin may synergistically interact to control long-term feeding. (C) 1997 Elsevier Science Inc.