The objectives of this study were to test the hypothesis that alcohol can cause reactive hypoglycemia by attenuating the release of counterregulatory hormones. The subjects were eight healthy volunteers (five men and three women, aged 20-40 yr). Each subject drank, using a randomized, double blind design 1) three large gin with regular tonics (0.5 g/kg alcohol and 60 g carbohydrate, mainly sucrose (G+T); 2) the same amount of alcohol with Slim-line tonic (0.5 g carbohydrate; G alone); and 3) regular tonic without alcohol (T alone). Glucose, insulin, and counterregulatory hormone levels and middle cerebral artery velocity (MCAV), an index of cerebral blood flow, were measured. Alcohol levels averaged 60-70 mg/dL. Peak insulin levels were similar in both studies in which regular tonic was consumed (95% confidence interval for difference, -6 to 22 microU/mL). After the ingestion of G+T, the blood glucose nadir was lower compared to that with T alone (3.35 vs. 3.87 mmol/L; P < 0.02) or G alone (3.35 vs. 3.95 mmol/L; P < 0.01). After drinking gin, subjects reported typical hypoglycemic warning symptoms unrelated to the prevailing glucose level. In both alcohol studies, there was marked blunting of GH release (P < 0.01). Despite a blood glucose nadir of 3.35 mmol/L, plasma epinephrine levels rose only slightly from 267 to 455 pmol/L (P = NS) after G+T. Ingestion of alcohol also caused a transient rise in right MCAV (P < 0.05) followed by a late drop in velocity in both cerebral hemispheres in the G+T study (P < 0.05). In otherwise healthy individuals a combination of gin and regular tonic can induce reactive hypoglycemia. Acute ingestion of alcohol impairs the epinephrine response and markedly suppresses the release of GH in response to a fall in blood glucose levels.