Forty-eight patients undergoing transphenoidal removal of pituitary tumors received submucosal injections of epinephrine in saline solution during halothane, enflurane, or isoflurane anesthesia. Twelve additional patients received epinephrine in 0.5 percent lidocaine while anesthetized with halothane. Positive evidence of ventricular irritability was given by the appearance of 3 or more premature ventricular contractions during or following injection. Positive or negative responses were plotted against the total dose of epinephrine in mug/kg body weight. From these data, the dose producing a positive response in 50 percent of patients (ED50) was calculated. An ED50 of 2.1 mug/kg for halothane, 3.7 mug/kg for halothane-lidocaine, 10.9 mug/kg for enflurane, and 6.7 mug/kg for isoflurane indicates the relative safety of these agents when epinephrine is injected for hemostasis. The data also suggest that lidocaine given with the epinephrine protects against ventricular arrhythmias.