Chronic treatment with leptin regulates body weight and energy balance and reduces food intake in obese and lean mice. In 18- to 20-h fasted lean mice (C57BL/6, +/+), we examined the acute effect of a single intraperitoneal injection of recombinant mouse leptin (0.12 mg/kg) on food intake and gastric emptying. Leptin reduced food intake, with a peak inhibition at the 5th h postinjection (69 +/- 12%/h), although there was no change in food consumption at the 1st h. Leptin did not alter the 4-h rate of gastric emptying of a solid nutrient meal (free access to Purina chow for either 1-, 2-, or 4-h period). In normal Sprague-Dawley rats fasted for 18-20 h, a single intraperitoneal injection of recombinant mouse leptin (0.2 or 1.2 mg/kg) did not modify the 7-h cumulative or hourly food intake. These results show that a single intraperitoneal injection of recombinant mouse leptin reduces food intake within 5 h while not influencing gastric emptying of ingested food in lean mice. Sprague-Dawley rats are unresponsive to the food intake-reducing effect of a single intraperitoneal injection of mouse leptin at a dose 10-fold higher than that shown to be effective in mice within the first 4-7 h postinjection.