We examined the relationship between gastric HCO3- and Na+ secretion under fasting and sham-fed conditions in nine healthy men and also evaluated the effect of the carbonic anhydrase inhibitor acetazolamide on gastric secretion of HCO3- and Na+. Secretion of H+, K+, and Cl- were also measured. Gastric HCO3- secretion rates under fasting and sham-fed conditions closely paralleled Na+ secretion rates. A maximally tolerated intravenous dose (10 mg/kg) of acetazolamide significantly inhibited H+, Cl- and K+ secretion but did not significantly affect Na+ or HCO3- secretion. Thus the gastric mucosa secretes HCO3- and Na+ in parallel in humans both under fasting and sham-fed conditions. Relative to parietal secretion of HCl, nonparietal secretion of HCO3- and Na+ is resistant to carbonic anhydrase inhibition.