A combination of medetomidinetiletamine-zolazepam was used to conduct six immobilizations of free-ranging lions (Panthera leo) in Waza National Park, Cameroon, during 1999 and 2000. Drugs were administered by dart injection at 0.07±0.01 (mean±SD) mg/kg of medetomidine and 1.8±0.5 mg/kg of tiletamine-zolazepam. Chemical immobilization was characterized by smooth inductions (14.1±6 min), satisfactory analgesia, and muscle relaxation. One animal was treated for bradypnea. No major alterations of physiologic parameters (heart and respiratory rates, rectal temperature) were seen during immobilization in the other lions. Relative arterial oxygen saturation was measured in two animals and revealed mild hypoxemia. The animals received atipamezole at 0.3±0.1 mg/kg intramuscularly for reversal of anesthesia. Recoveries were uneventful. All animals were radiocollared, and no mortalities occurred during an 18-mo follow-up period. Use of medetomidine-tileta-mine-zolazepam for anesthesia and reversal of anesthesia with atipamezole appear to be useful for reversible immobilization of free-ranging lions.