The cognitive potential, P300, is a phenomenon frequently studied in relation to template matching of the brain. To understand the neurochemical mechanisms of its generation, we compared the effects of three antidepressants, fluoxetine, tianeptine and clomipramine after single and repeated application as well as after 1 week of withdrawal on the P300 and N200 waves in an auditory 'odd-ball' paradigm in three parallel groups of 10 healthy volunteers. Following single administration, both fluoxetine and clomipramine reduced (-39 +/- 14%, p < 0.01) the peak amplitude of P300 at the Pz electrode. For fluoxetine and tianeptine, reduced amplitudes of 19 +/- 7% and 24 +/- 11%, respectively, were found following 8 days of treatment, 2 h after administration. However, for clomipramine no additional diminution was found on day 8 with respect to day 1. Topographic distributions tended to be significantly modified at the frontal scalp area 1 h after the tianeptine administration on day 8, whereas the postdosing changes induced by fluoxetine were localised in the midline and right centrotemporal scalp regions. Only minor reductions in peak latencies have been observed. It can be concluded that serotonin selective drugs have a slower onset of P300 amplitude decrease than clomipramine, which has additional effects on monoaminergic and on cholinergic systems. These results suggest that serotonin has a regulatory function in the neurotransmission of cerebral structures which are involved in the evaluation of stimulus relevance.