We studied the effect of ranitidine given in graded bolus intravenous doses on gastric acid hypersecretion in an unfed 3-month-old male with short bowel syndrome. We measured gastric volume and H+ serially for 12 h following each bolus and correlated inhibition of H+ secretion with plasma ranitidine concentration. In the first 4 h post drug, doses of 0.3, 1.0, 2.0, and 4.0 mg/kg resulted in 78, 93, 97, and 98% inhibition, respectively. The cumulative 12-h effect of the drug was to inhibit H+ secretion 67, 63, 72, and 87%. The IC50 for H+ secretion was between 50 and 100 ng/ml, and the IC90 between 130 and 150 ng/ml. Volume of gastric secretions was reduced by approximately 50% by all ranitidine doses. Because gastric acid hypersecretion interferes with nutrient absorption, the infant was treated with ranitidine during a 5-week trial of enteral feeding. A decrease in the antisecretory effect of ranitidine apparent at the end of the treatment period temporally related to an increase in oxyntic mucosal function. No adverse drug effects were observed during treatment.