Binding of [3H]D-aspartate, as an indicator of glutamate uptake sites, was investigated in post-mortem human brain tissue by use of a centrifugation assay to separate free and bound ligand. Binding was displaceable, apparently saturable and to a single site, with mean KD and Bmax values of 2.3 microM and 40.3 nmol/g tissue in the frontal cortex. The method was applied to the study of tissue from frontal and temporal cortices and the caudate nucleus of five psychiatric patients who had undergone a frontal leucotomy. The effects of this neurosurgical procedure were to diminish by almost 50% the density of D-aspartate binding sites in the frontal cortex and caudate nucleus, while the temporal cortex was less affected. It is concluded that the method provides a potentially useful correlate of glutamatergic innervation in human brain tissue.