Gastric secretion (volume, pepsin and acid output) was measured in the basal state and during graded doses of intravenous pentagastrin (0.02,0.2 and 2 µg/kg/h) in 5 patients with moderate to severe renal failure. On one occasion they also received intravenous cimetidine (1.5 mg/kg bolus followed by 0.5 mg/kg/h). Sustained cimetidine concentrations of approximately 2 µg/ml (8 nmol/ml) were associated with a 75–90% inhibition of stimulated acid output, reflecting both a reduction in volume and a lower acid concentration. Pepsin output was less depressed by cimetidine, as the pepsin concentration of the gastric juice actually increased in response to combined pentagastrin and cimetidine administration. It is concluded that renal failure, although affecting cimetidine pharmacokinetics, does not appreciably alter the response to the d