Urinary acidification was studied in six unrelated infants with fetal alcohol syndrome and eight healthy age-matched infants. Creatinine clearance, fractional sodium excretion, plasma renin activity, and plasma aldosterone were normal in all patients but fractional potassium excretion was lower in the patients than in the controls (p = 0.0001). After ammonium chloride loading, minimum urine pH was significantly higher in FAS patients than in control subjects (5.5 +/- 0.1 and 4.7 +/- 0.1, respectively, p = 0.00005). Net acid excretion was also lower in the patients (24.5 +/- 1.7 Eq/min) than in the controls (27.8 +/- 2.1 Eq/min, p = 0.008). Following sodium bicarbonate loading, fractional bicarbonate excretion was significantly higher (p = 0.00005) and fractional potassium excretion significantly lower (p = 0.002) in the patients than in the controls with comparable blood pH and bicarbonate levels. Treatment with chlorothiazide lowered plasma potassium and raised plasma bicarbonate to normal levels (p = 0.05). Concomitantly, fractional sodium excretion, fractional potassium excretion, and urinary net acid excretion increased significantly (p = 0.01). We conclude that patients with fetal alcohol syndrome have a defect in distal acidification and potassium excretion which cannot be attributed to abnormal aldosterone secretion.