The effect of indomethacin, theophylline, and progranolol on ethanol augmentation of insulin secretion after intravenous glucose stimulation was studied. Intravenous glucose tolerance tests were performed with and without pretreatment with oral ethanol. The role of indomethacin was evaluated in six healthy subjects; the effect of theophylline and propranolol on ethanol augmentation in insulin secretion was studied in five and six subjects, respectively. Ethanol pretreatment was followed by increased insulin (P < .01) and C-peptide areas (P < .01) after intravenous glucose (Area, 0 to 20 minutes). Indomethacin suppressed the ability of ethanol to augment insulin (P < .01) and C-peptide (P < .01) responses. Neither theophylline nor propranolol affected ethanol augmentation of insulin secretion. In conclusion, indomethacin probably interferes with the mechanism for ethanol augmentation of glucose-induced insulin secretion. It is suggested that inositol phospholipids take part in the effect of ethanol to augment insulin secretion, and that indomethacin interferes with the metabolism of inositol phospholipids. © 1992.