Immunosuppressants are administered chronically with other pharmacological agents such as antihypertensives, antifungals, antibiotics, and steroids. Preliminary studies indicate that FK 506 significantly alters hepatic drug metabolism.1–3 Alterations in hepatic metabolism of a coadministered drug may affect the pharmacokinetics and pharmacodynamics of the other drug. Thus far, no studies have investigated the effect of FK 506 administration on the pharmacological effect of a concurrently administered drug. The objective of this study was to investigate the effect of various routes of administration and different administration regimens of FK 506 on the pharmacodynamics of pentobarbital.