Ranitidine, an H2-receptor antagonist, has been shown to reduce pentagastrin-stimulated gastric secretion. We examined the relationship between inhibition of gastric secretion and ranitidine serum concentration. Twelve normal male subjects received 20, 40, or 80 mg of ranitidine orally 90 min before starting a 3-hr continuous infusion of pentagastrin, 2 micrograms/kg/hr. Ranitidine, 20, 40, and 80 mg, reduced hydrogen ion output by 29%, 50%, and 70% and secretion volume by 21%, 37%, and 47%. Pepsin activity was reduced by 8%, 50%, and 49% by the same doses. Peak serum concentration was correlated positively with percent reduction in hydrogen ion output (r = 0.81, P less than 0.001) and volume (r = 0.71, P less than 0.01) over a 2-hr period. A 50% inhibition of hydrogen ion output was associated with a peak ranitidine serum concentration of 165 micrograms/l and subjects reached peak serum concentration 60 to 120 min after oral dosing. An appropriate therapeutic effect should be achieved with 8 hourly doses of 80 mg ranitidine. No clinically significant subjective or toxic biochemical effect of ranitidine was seen after single doses. White blood cell count was reduced in 11 of 12 subjects 7 days after ranitidine, an observation which calls for further investigation.