Study Objective: To compare a total intravenous (IV) anesthetic technique based on propofol and alfentanil with a commonly used anesthetic technique for craniotomy. Design: Open-label, randomized, clinical study. Setting: Neurosurgical clinic at a university hospital. Patients: Forty patients, aged 18 to 55 years, scheduled. for brain tumor surgery. Interventions: In 20 patients, anesthesia was induced with fentanyl and thiopental sodium and maintained with fentanyl, dehydrobenzperidol, isoflurane, nitrous oxide (N 2O), and a thiopental sodium infusion. Twenty patients were anesthetized with a propofol loading infusion followed by a maintenance infusion at a fixed rate. In addition, alfentanil was administered as a. loading bolus, followed by a variable-rate infusion, with additional doses as necessary to maintain hemodynamic stability. Measurements and Main Results: A decrease in blood pressure (BP) after induction with thiopental sodium was followed by a significant increase in BP and heart rate (HR) during intubation. BP and HR did not change during the propofol loading infusion. However, the administration of alfentanil was followed by a similar decrease in BP with a return to baseline values during the intubation period. Return of normal orientation (7 ± 5 minutes vs 27 ± 23 minutes) and concentration (12 ± 12 minutes vs 35 ± 37 minutes) was shorter and more predictable for the propofol-alfentanil—treated patients than for the thiopental sodium patients. Maintenance propofol concentration (nine patients) was between 3 ±0.69 μg/ml and 3.36 ± 1.17 μg/ml, while the concentration at awakening was 1.09 μg/ml. Alfentanil concentration at extubation (nine patients) was 79 ± 34 ng/ml. Conclusion: A total IV anesthetic technique with propofol and alfentanil is a valuable alternative to a more commonly used technique based on thiopental sodium, N 2O fentanyl, and isoflurane.