The effect of concurrent ranitidine administration on the disposition of pethidine was investigated in eight healthy male volunteers (19-33 years). The subjects received 70 mg i.v. pethidine HCl doses before and during ranitidine treatment (150 mg p.o. twice daily). Ranitidine therapy was not associated with significant alterations in pethidine elimination rate constant, volume of distribution at steady state, total body clearance, and 24 h urinary excretion. No alteration in pethidine oxidation to norpethidine was noted, as suggested by nonsignificant changes in lag time to appearance of quantifiable norpethidine in serum, time to peak concentration, peak concentration, area under the curve from time 0.24 h, and 24 h urinary excretion. It would appear that, unlike cimetidine, ranitidine does not interact pharmacokinetically with pethidine. Further studies are necessary to evaluate the potential clinical advantages of ranitidine vs cimetidine therapy in patients also receiving pethidine.