Two adult California sea lions (Zalophus californianus) were effectively anesthetized 13 times with medetomidine (0.010–0.013 mg/kg), midazolam (0.2–0.26 mg/kg), and butorphanol (0.2–0.4 mg/kg) by i.m. hand or pole syringe injection. For each anesthetic event, atropine (0.02 mg/kg, i.m.) was administered 6–20 min after initial injections, and oxygen administration via face mask or nasal insufflation began at the same time. Light anesthesia was induced in 8–22 min and lasted 13–78 min. During eight of the procedures, isoflurane (0.5–2.0%) was administered via face mask or endotracheal tube for an additional 30–120 min to facilitate longer procedures or surgery. Anesthesia was antagonized with atipamezole (0.05–0.06 mg/kg) and naltrexone (0.1 mg/kg) in seven events, with the addition of flumazenil (0.0002–0.002 mg/kg) in six events. The antagonists were administered by i.m. injection 42–149 min after administration of the induction agents. All sea lions recovered to mild sedation within 4–17 min after administration of the antagonists.