The regional distribution and properties of the sodium-independent "specific" binding of [3H]GABA to membranes prepared from human brains (control and Parkinsonian patients) have been investigated. The affinity of [3H]GABA for the binding site was similar for human cerebellar cortex (Kd = 3.4 x 10(-7) M) and whole rat brain brain (Kd = 5.1 x 10(-7) M) and was inhibited by bicuculline (ID50 = 2.2 X 10(-5) M). In the normal human brain the cerebellar cortex demonstrated the highest number of binding sites, in accordance with the large number of GABA interneurons in this structure. The hippocampus also displayed a high capacity to bind [3H]GABA, whereas cerebral cortical areas showed a lesser capacity. [3H]GABA binding was similar in many regions of the basal ganglia (amygdala, putamen, caudate or accumbens) but was lower than that for the cortical regions. The binding of [3H]GABA to membranes from the substantia nigra, thalamus and internal or external pallidum was lower than for the above regions. Subcortical white matter did not exhibit specific binding for [3H]GABA. In membranes prepared from Parkinsonian patients [3H]GABA binding was greatly decreased in the substantia nigra, but not in other brain areas examined. From this observation it was concluded that there are [3H]-brain areas examined. From this observation it was concluded that there are [3H]-GABA binding sites on the cell bodies (or dendrites) of the nigral dopamine neurons.