The pharmacokinetics of alfentanil were studied after single dose intravenous administration of 125 μg/kg to 19 intensive care unit patients who were divided into 3 groups. Group I was given oral antacid, and groups II and III were given, respectively, cimetidine 1200 mg/day IV and ranitidine 300 mg/day IV for 48 hours before administration of alfentanil. Alfentanil plasma concentrations were determined over the 8 hours following drug administration using a radio-immunoassay. Pharmacokinetic parameters were calculated using a noncompartmental analysis. In group II, alfentanil plasma concentrations were significantly higher than in the other groups. In addition, significant changes involving the elimination half-life (142.3 ± 35 vs 81.14 ± 11 and 88.1 ± 33 minutes), total clearance (1.27 ± 0.5 vs 3.56 ± 1.17 and 2.74 ± 1 ml/kg/min) and total volume of distribution related to the pseudo distribution phase (226 ± 73 vs 336 ± 76 and 271 ± 61 ml/kg) were found in group II vs groups I and III. These results suggest that pretreatment with cimetidine alters alfentanil pharmacokinetics after single dose administration. In contrast, ranitidine does not appear to have a significant effect.