The gut peptide CCK is a nutrient-related signal important to the control of food intake. In the present studies, we observed that a single intraperitoneal injection of CCK (1-2 microgram/kg) given 2-3 h after intracerebroventricular leptin (2-5 microgram) reduced body weight and chow intake over the ensuing 48 h more than did leptin alone. CCK alone had no effect on either 48-h chow intake or body weight but significantly reduced feeding during a 30-min sucrose test. However, reduction of 30-min sucrose intake by CCK was not enhanced by prior intracerebroventricular leptin. The present data suggest that CCK can contribute to the regulation of body weight when central leptin levels are elevated.