We recently developed a flexible, portable, computer-based neurobehavioral evaluation system (NES) to standardize data collection in epidemiologic field studies of individuals at risk for neurobehavioral toxicity. The current study was performed to examine the system's sensitivity to subtle neurobehavioral impairment induced pharmacologically in normal subjects. Twelve men 18 to 36 years old were tested with the NES three times, in an initial training session followed by separate drug and control sessions in randomized order. During drug sessions subjects received a combination of 20% nitrous oxide and 80% oxygen through a nasal mask. In control sessions subjects received 100% oxygen. Nine NES tests evaluating psychomotor performance, visuospatial ability, memory, and mood were administered in approximately 40 minutes. Nitrous oxide exposure impaired performance on three tests: continuous performance, symbol-digit substitution, and finger tapping. Another test, pattern memory, showed a trend toward impairment, while the remainder were not affected by the drug. These data are consistent with previous reports that the threshold effect of nitrous oxide is a decrement in psychomotor speed. The findings indicate that our NES is sensitive to short-term impairment in central nervous system function of the type induced by a number of neuroactive agents. In view of its efficiency in data acquisition and analysis, computerized neurobehavioral testing appears to be a very promising method for evaluation of effects of a wide range of pharmacologic agents.