SummaryDisease states, including end‐stage kidney or liver failure, can alter the protein binding of various drugs in children. The plasma protein binding of alfentanil was evaluated in blood samples from 15 children about to undergo kidney transplantation, 21 children undergoing liver transplantation, and 28 otherwise healthy children undergoing elective surgery. Compared with the healthy children, patients with kidney disease had a significant decrease in protein binding (89.2%± 5.4 v. 93.1%± 3.2), an increase in α1‐acid glycoprotein concentration (108.8 mg·dl−1± 44.3 v. 71.8 mg·dl−1± 30.7), and no change in albumin concentration (3910 mg·dl−1± 754 v. 4555 mg·dl−1± 524); whereas patients with liver disease had a significant decrease in protein binding (85.9%± 6.2 v. 93.1%± 3.2), no change in α1‐acid glycoprotein concentration (65.8 mg·dl−1± 31.8 v. 71.8 mg·dl ± 30.7), and a decrease in albumin concentration (3045 mg·dl−1± 1255 v. 4555 mg·dl−1± 524). Because alfentanil is highly protein bound, even small changes in the drug's free fraction could have marked pharmacodynamic effects