OBJECTIVE: To compare the anesthetic index of sevoflurane with that of isoflurane in unpremedicated dogs. DESIGN: Randomized complete-block crossover design. ANIMALS: 8 healthy adult dogs. PROCEDURE: Anesthesia was induced by administering sevoflurane or isoflurane through a face mask. Time to intubation was recorded. After induction of anesthesia, minimal alveolar concentration (MAC) was determined with a tail clamp method while dogs were mechanically ventilated. Apneic concentration was determined while dogs were breathing spontaneously by increasing the anesthetic concentration until dogs became apneic. Anesthetic index was calculated as apneic concentration divided by MAC. RESULTS: Anesthetic index of sevoflurane (mean +/- SEM, 3.45 +/- 0.22) was significantly higher than that of isoflurane (2.61 +/- 0.14). No clinically important differences in heart rate; systolic, mean, and diastolic blood pressures; oxygen saturation; and respiratory rate were detected when dogs were anesthetized with sevoflurane versus isoflurane. There was a significant linear trend toward lower values for end-tidal partial pressure of carbon dioxide during anesthesia with sevoflurane, compared with isoflurane, at increasing equipotent anesthetic doses. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that sevoflurane has a higher anesthetic index in dogs than isoflurane. Sevoflurane and isoflurane caused similar dose-related cardiovascular depression, but although both agents caused dose-related respiratory depression, sevoflurane caused less respiratory depression at higher equipotent anesthetic doses.