The effect of intravenous administration of two sedatives, diazepam (0.3 mg/kg) and thiopental (6.0 mg/kg), on the vestibulo-ocular reflex (VOR) in man was investigated on 9 volunteers. The VOR was evoked with a velocity step rotation test and gain and time constant of prerotatory and postrotatory nystagmus were measured. Both drugs reduced VOR gain. Diazepam-induced reduction lasted 8 h and thiopental-induced reduction 1 h. A reduction of the VOR time constant was found lasting about 1 h for both drugs, but with a tendency for the thiopental effect to last longer. These findings, not previously described in man, differ from what has been found in macaques and rabbits injected with diazepam. The reduction of gain and time constant were not correlated with the blood concentration of either drug. The present results suggest that in man the VOR gain and time constant are both reduced by different types of sedatives although with different time courses. On the basis of previously shown effect of alertness on the VOR, it is hypothesized that diazepam and thiopental, besides having a specific effect on central nervous system structures important to the VOR, also induce reduction of the VOR through a general sedation of the CNS.