The present study was conducted to investigate the action of serotonin (5-HT) on synaptic transmission within local circuits of the rat somatosensory cortex. Responses of single somatosensory cortical neurons to activation of excitatory and inhibitory synaptic pathways or iontophoretic application of putative neurotransmitters were examined before, during and after microiontophoresis of 5-HT. Monoamine-induced changes in neuronal responsiveness were quantitatively assessed by computer-based analysis of peri-event histograms. 5-HT typically exerted a differential inhibitory effect on neuronal firing, such that stimulus-induced responses were reduced relative to spontaneous discharge. In 16 of 24 (67%) of the cells tested, 5-HT depressed synaptically evoked excitation more than background firing such that "signal to noise" ratio was decreased. In some cases evoked spiking was reduced from control levels at doses of 5-HT subthreshold for producing direct depression of baseline firing rate. Cortical neuron excitatory responses to iontophoretically applied acetylcholine (8 of 13 cells) and glutamate (10 of 15 cells) were also reduced during microiontophoresis of 5-HT. A similar reduction in inhibitory efficacy was observed in 62% of the cases (10 of 16 cells) where 5-HT was interacted with GABA-induced depressant responses. Local administration of 5-HT also resulted in an antagonism of stimulus bound inhibition of firing (9 of 11 cells). These results are contrasted with previously observed facilitory effects of norepinephrine (NE) on cortical neuronal responsiveness to afferent synaptic inputs and putative transmitter agents. It is suggested that endogenously released 5-HT and NE may exert complementary modulatory-type actions on neuronal responsiveness as a means of regulating the transfer of sensory information through local cerebrocortical circuits.