Serotonin-1 receptors were examined in post-mortem human brains, using quantitative in vitro autoradiography. [3H]Serotonin was used as a ligand. Serotonin-1 receptor subtypes were defined with 8-hydroxy-2-(di-n-propylamino)-tetralin and mesulergine. In the control human basal ganglia, the highest density of serotonin-1 binding sites was observed in both lateral and medial globus pallidus and substantia nigra reticulata. Lower densities were seen in the substantia nigra pars compacta, the nucleus accumbens, caudate and putamen. The majority of these serotonin-1 sites belonged to the serotonin-1D class. No significant alteration of the density and distribution of these sites was observed in Parkinson's disease brains. In contrast, a marked decrease in the density of the receptor binding was seen in the basal ganglia and the substantia nigra from patients dying with Huntington's disease. These results suggest that serotonin-1D receptors are expressed by cells intrinsic to the striatum which degenerate in Huntington's disease and project to the substantia nigra reticulata where these receptors are probably presynaptically localized. These observations in pathological human brains agree with the results of lesion studies in animal models and further support a role for serotoninergic mechanisms in movement control.