The aim of the present study was to compare the influence of volatile anesthetics on transcranial motor-evoked potentials (tcMEP) in humans anesthetized with propofol/fentanyl/nitrous oxide and on partial neuromuscular blockade (NMB). The authors studied 35 ASA I and II patients who were undergoing elective craniotomy and brain tumor resection. The patients were randomized to one of three groups to receive halothane (HAL), isoflurane (ISO), or sevoflurane (SEV). Anesthetic depth was initially adjusted using the bispectral index to 40±5, and NMB was adjusted to 40%–50% of one twitch of train of four (T1) after recovery from intubation. MEPs with train of five square-wave pulses were elicited using screw electrodes placed in the skull over C3–C4. After craniotomy, the inhalational agent was introduced at 0.5 MAC and then 1.0 MAC (20 minutes each), and the effects on MEPs, NMB, and hemodynamic variables were studied. A decrease in BIS and systolic blood pressure was observed with all agents. Both SEV and ISO at 1.0 MAC significantly decreased train-of-four ratio from 38.4±18.1 at control to 19.0±9.7 and from 35.3±12.4 to 26.1±13.7, respectively (P<0.001), but not HAL at 1.0 MAC. The amplitudes of tcMEPs were significantly reduced by all agents at 1.0 MAC, with the effect being less in HAL at 0.5 MAC. We have shown that HAL had a lesser suppressive effect on MEPs than either ISO or SEV at 0.5 MAC, which was partially due to a lesser degree of NMB.