The molecular effects of droperidol (C22H22FN3O2) on single sodium channels from the human brain were investigated using the electrophysiological planar lipid-bilayer technique. Droperidol (0.05–0.8 mm) induced a concentration dependent and voltage independent reduction in the time averaged single channel conductance by two mechanisms: a reduction in the fractional channel open time (major effect, approximately 90%) and a decrease in the channel amplitude (minor effect). The weighted computer fit of the concentration response for the combined effect curve yielded an EC50 of 0.68 mm droperidol and a maximal conductance block of 77%. These blocking effects of droperidol on CNS sodium channels occurred at a concentration range comparable with other specific anaesthetic compounds but far beyond clinical serum levels (up to 0.002 mm). Therefore in contrast with animal preparations (frog peripheral nerve, sodium channel) the human brain sodium channel is not a major target site for droperidol during clinical anaesthesia.