A growing number of studies demonstrate that antagonists of the N- methyl-D-aspartate (NMDA) receptors can induce a broad range of psychophysiological anomalies in healthy subjects similar to those observed in schizophrenia. In this study, the effect of a sub-anaesthetic dose of the non-competitive NMDA antagonist, ketamine, on human selective attention was explored. It was hypothesized that ketamine would induce in healthy subjects psychophysiological anomalies that are commonly observed in schizophrenic patients, such as reduced P300 amplitude and a reduction of both mismatch negativity (MMN) and processing negativity (PN). In a double-blind randomized placebo-controlled design, healthy male volunteers (n = 18) were challenged with a sub-anaesthetic dose of ketamine (0.3 mg/kg iv) after which they were tested in a selective attention task. In this task, two types of stimuli were evenly presented to the left or right ear: standard tones (80%) and deviant tones (20%) of either 1000 or 1100 Hz. The duration of a stimulus (95 dB) was 50 ms, the interstimulus intervals were randomized between 1750 and 2150 ms. The volunteer was instructed to push a button as quickly as possible after hearing the deviant tone in a specified ear. Ketamine did not alter performance of the subjects: in both the placebo and drug condition their reaction times for and percentages of hits and false alarms did not differ. Ketamine did, however, reduce PN and the P300 amplitude (both in general and to deviant stimuli in particular). However, no drug effect on MMN was found. In addition, ketamine enhanced the N100 amplitude to deviant stimuli. In conclusion, ketamine induces some of the attentional deficits in healthy controls that are observed in schizophrenic patients. Consequently, reduced glutamatergic activity in the brain may be involved in some of the symptoms of schizophrenia. (C) 2000 American College of Neuropsychopharmacology.