The high-affinity binding of 3H-serotonin and 3H-DPAT was studied in membrane preparations and tissue sections of cerebral cortex and basal ganglia of human brain. In tissue sections, 3H-serotonin bound to sites present at high density in the cerebral cortex, hippocampus and basal ganglia. 3H-DPAT bound predominantly to the outer layers of the cerebral cortex and the hippocampus, no significant binding was observed in the basal ganglia. In cortical membranes 3H-serotonin bound to a heterogeneous population of sites, one of which was similar to a binding site labelled by 3H-DPAT (the putative 5HT-1A receptor). 3H-serotonin binding to membranes prepared from the putamen displayed low affinity for DPAT, mesulergine and spiperone, RU24969 was considerably less potent than serotonin itself. This 3H-serotonin binding site does not have the properties of those sites described in rodent brain (5HT-1A, 5HT-1B, and 5HT-1C), and may represent a novel serotoninergic binding site.