The effect of the intravenous infusion of peptide p-Glu-His-Ala-OH, analog of the postulated anorexigenic peptide, on the insulinaemic response to an intravenous bolus of 20 g glucose was studied in 6 obese patients (body mass index 43.12 +/- 5.77 kg/m2). The infusion of the peptide reduced the insulinaemic response (p < 0.05) without modifying either the C-peptide or the glucose response. This decreased insulinaemic response is associated with a greater hepatic extraction of insulin (86.45 +/- 1.1% vs 82.1 +/- 1.2%; p 0.05), determined in terms of the molar ratio of the C-peptide to insulin) but not with a smaller pancreatic secretion (determined as C-peptide levels). Our results confirm that the infusion of the peptide increases the hepatic insulin extraction without its effect being mediated by any intestinal factor. Its therapeutic application remains to be determined.