We examined the effects of exogenous and endogenous GIP on plasma triglyceride levels in rats, pretreated with a fat-enriched diet, during intraduodenal infusion of a lipid test meal (Lipomul, 8 ml/h). Following the fat load the plasma triglyceride levels increased nearly linearly from a fasting value of 0.621 +/- 0.031 mmol/l to 3.32 +/- 0.403 mmol/l at 150 min. Simultaneously, the plasma GIP levels rose from 47.1 +/- 5.1 at fasting to a peak value of 268.4 +/- 32.2 pmol/l at 120 min. When porcine GIP was infused intravenously during the fat load, the plasma triglyceride increments were significantly smaller (control 1.64 +/- 0.264 mmol/l versus 0.949 +/- 0.114 mmol/l during GIP infusion at 60 min; p less than 0.002). GIP infusion in the absence of the fat load did not change fasting triglyceride levels. The effect of endogenous GIP was investigated by neutralization of GIP by injection of GIP antiserum (0.3 ml). Rats pretreated with the antiserum exhibited a significantly greater triglyceride increment late in the time course of the fat load. These data demonstrate that exogenous and endogenous GIP are able to lower the plasma triglyceride response to a fat load. Both, inhibition of fat absorption or stimulation of triglyceride uptake by peripheral tissues may be responsible for the GIP effects. The gut peptide GIP seems to represent an important hormonal regulator of postprandial triglyceride response.