The suppression of food intake elicited in rats by injection of pancreatic glucagon and the accompanying changes in energy metabolite flux were investigated. Glucagon injections, 120-360 micrograms ip, were made as rats began the first meal of the dark phase after food deprivation during the light phase. Glucagon-injected rats terminated their meals sooner and ate smaller meals than vehicle-injected rats. For metabolic assays, rats were identically treated and killed just at meal onset or 15 min later. Portal vein blood glucose increased similarly in all rats allowed to feed, whereas plasma nonesterified fatty acid and D-(-)-3-hydroxybutyrate levels decreased during feeding. In contrast, hepatic vein and aorta blood glucose levels increased more after glucagon than after vehicle injections. Liver glycogen content decreased after glucagon injections. The highest glucagon dose only had slight lipolytic and ketogenic effects. It was concluded the glycogenolytic and hyperglycemic action of glucagon may generate a satiety signal sufficient to cause premature termination of meals. Changes in ketone and lipid fluxes do not appear necessary for this behavioral effect.