In a double-blind, randomized, placebo-controlled study, the pharmacokinetics of alprazolam and its active metabolite, alpha-hydroxyalprazolam, were determined in 12 normal subjects and 12 dialysis patients [7 hemodialysis (HD) patients and 5 continuous ambulatory peritoneal dialysis (CAPD) patients]. Blood samples were collected over 48 hours after alprazolam 0.5 mg and alprazolam 2 mg administration. Alprazolam and alpha-hydroxyalprazolam concentrations and alprazolam free fraction were determined. The pharmacokinetics of alprazolam were similar in normal subjects and HD patients with the exception of higher free fraction in HD patients. Differences were detected, however, in the pharmacokinetics of alprazolam in CAPD patients when compared with normal subjects and HD patients. These differences included a higher free fraction and a lower apparent oral clearance and free clearance in CAPD patients than in normal subjects or in HD patients. There was also a tendency for a later Tmax and a longer elimination half-life in CAPD patients than in normal subjects or HD patients. Alpha-hydroxyalprazolam concentrations were less than 15% of corresponding alprazolam concentrations in normal subjects and dialysis patients. Thus, end-stage renal disease is associated with changes in absorption, distribution, and/or elimination of alprazolam.