Previous studies suggest that the rate of rise of the plasma glucose-dependent insulinotropic peptide (GIP) concentration, rather than the steady state level achieved, may be the stimulus of the increased insulin secretion that occurs when fat is ingested with carbohydrate. To test this hypothesis six normal men were given a 5-g iv bolus dose of glucose 15 min after a carbohydrate meal with or without fat. At the time of the iv glucose injection after the fat-containing meal, the rate of rise of plasma GIP was maximum, but the level was only 40% of the achieved by 30 min. Plasma GIP did not change after the meal without fat. After the fat meal, peak insulin and C-peptide levels in response to iv glucose were 60% greater than those after carbohydrate alone despite similar peak blood glucose levels. The calculated insulin clearance was not altered by the fat meal. We conclude that glucose-stimulated insulin secretion is increased early after fat ingestion, possibly due to a rise in GIP or other incretins.