Ten obese and 10 control subjects were studied in basal conditions and after ingestion of a standard mixed test meal. Blood glucose, insulin, somatostatin (SLI) and vasoactive intestinal polypeptide (VIP) concentrations were determined before and 30, 60, 90, 120, 180 and 240 min after the start of the meal. Basal SLI levels in the obese (14.4 ± 0.7 ng/l) were not significantly different from those in the controls (15.5 ± 0.8 ng/l), whereas after the meal a blunted secretory response was recorded. Baseline plasma VIP levels were higher in the obese (29.7 ± 1.5 ng/l) than in the control subjects (19.8 ± 1.3 ng/l) and, similarly to the controls, were unaffected by meal ingestion. Data suggest that in the course of obesity an enhanced VIP secretion in association with a diminished SLI responsiveness to meals occurs.