The role of the liver and the kidney in alfentanil metabolism has not been defined. The effects of cholestatic hepatic disease and chronic renal failure on the pharmacokinetics of alfentanil were evaluated in 9 children undergoing liver transplantation and 10 children undergoing kidney transplantation. These findings were compared with data from 10 children with normal hepatic and renal function undergoing other surgical procedures. There was no statistical difference among the 3 groups with respect to apparent volume of distribution, half-life, or clearance. In a subgroup of 3 patients undergoing liver transplantation alfentanil kinetics were determined both before and after the allograft was incorporated into the recipient's circulation. Though both volume of distribution and elimination half-life increased in the posttransplantation period, only the decrease in clearance was statistically significant. Thus, it appears that alfentanil may be a useful anesthetic agent in pediatric patients with cholestatic hepatic disease or chronic renal failure. The dose of alfentanil in these patients need not be altered except in the period immediately after liver transplantation.