The effects of a single dose of cyclosporine on anesthetic actions of pentobarbital and fentanyl were studied in mice. Mice given pentobarbital 2 hr after receiving cyclosporine, 60 mg/kg, slept a statistically significant 2.3 times longer than did controls. In a second study, each of two dose levels of cyclosporine was given before each of four dose levels of fentanyl. The analgesic effect of fentanyl, measured with the abdominal constriction test, was dose-dependent. Cyclosporine significantly increased the analgesia produced by fentanyl and did so in a dose-dependent manner. Cyclosporine by itself did not produce analgesia. Plasma levels of fentanyl and binding of fentanyl by plasma proteins were unchanged by cyclosporine treatment. The results show that a single dose of cyclosporine can increase pentobarbital hypnosis and fentanyl analgesia in mice but do not establish the mechanism of these interactions.