To examine the relationship between neurosteroids and vertigo we performed electrophysiological studies to determine whether pregnenolone sulfate (PS) affects the activity of medial vestibular nucleus (MVN) neurons in alpha-chloralose-anesthetized cats. Single neuronal activities in the MVN were recorded extracellularly using a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette. 3 mM PS, 1 M glutamate and 3 mM NaCl were applied microiontophoretically in the immediate vicinity of the target neurons. The effects of these drugs were then examined on type I and type II neurons, identified by their responses to horizontal and sinusoidal rotations. The iontophoretic application of PS dose-dependently increased the spontaneous firing of both type I and type II neurons. The larger increase in firing was observed in type I neurons as compared with type II neurons following the PS application. These results suggest that PS excites types I and II neurons differentially, presumably resulting in a disturbance of harmony of the vestibulo-ocular reflex with ensuing development of vertigo.