The effect of isoflurane alone (Group 1) and isoflurane following thiopental (Groups 2 and 3) on baroreflex control of heart rate in humans was investigated in this study. Phenylephrine (the pressor test) and sodium nitroprusside (the depressor test) were used to induce moderate changes in arterial blood pressure and to alter the stimulation of baroreceptor sites. In addition, graded neck suction was employed to examine carotid baroreflex control of heart rate. In Group 3 subjects, phenylephrine was infused continuously during anesthesia to maintain mean arterial blood pressure near control levels. The pressor- and neck-suction-derived baroreflex slopes were decreased progressively from awake to 1.0 and 1.5 MAC isoflurane. The slopes of the depressor responses were decreased at 1.0 MAC but showed little further depression at 1.5 MAC. For each method, the depression of baroreceptor slopes from control to 1.0 MAC and 1.5 MAC was similar among the three groups. Maintenance of arterial blood pressure (Group 3) and the utilization of thiopental (Group 2) did not significantly alter the depression of baroreflex responses during increasing levels of isoflurane anesthesia. Neck suction derived slopes compared favorably with the pressor test slopes (r = 0.75, P less than 0.001). This study indicates that the depression of arterial baroreflex heart rate responses under isoflurane anesthesia are less pronounced than the depression of baroreflex responses noted by other investigators for halothane or enflurane. The neck suction technique appears to be a sensitive method useful in assessing the carotid sinus reflex in awake and anesthetized humans.