Psychopharmacological activation, in conjunction with positron emission tomographic measurements of regional cerebral blood flow (rCBF), was used to investigate the neurotransmitter basis of a specific cognitive function in man. Monoaminergic neurotransmission was pharmacologically manipulated during performance of auditory - verbal memory tasks. Statistical parametric mapping was used to identify the brain sites of interaction between memory-induced increases in rCBF and active drugs. Memory task-induced increases in rCBF in the left prefrontal cortex were attenuated by apomorphine, a non-selective dopamine agonist, whilst buspirone, a serotonin1A partial agonist, augmented rCBF increases in this area. In addition, apomorphine and buspirone augmented memory-induced increases in rCBF centred in the posterior cingulate cortex, whilst buspirone alone attenuated rCBF increases in the retrosplenial cortex and posterior parahippocampal gyrus. These regionally selective interactions may represent neuromodulatory effects of monoaminergic neurotransmission on a specific cognitive function in man.