A clinical, morphological and neurochemical correlative study in patients with Parkinson's syndrome and Huntington's chorea is reported. In the former group of patients, 69 brains were examined morphologically and 28 biochemically; in the latter group, 4 brains were examined morphologically and 14 biochemically. The results were as follows: (1) The main morphological alteration common to all forms of Parkinsonism was damage to the substantia nigra with a loss of the melanin-containing nerve cells in the zona compacta; the degree and pattern of this cell loss varied in a manner characteristic of the different forms of Parkinsonism. (2) Neurochemically, Parkinson's syndrome was characterized by a decrease in the concentrations of dopamine (DA) and its metabolite homovanillic acid (HVA) in the striatum (caudate nucleus and putamen) and pallidum. (3) A satisfactory positive correlation could be established between the degree of cell loss in the zona compacta of the substantia nigra and the disturbance of DA metabolism in the nuclei of the basal ganglia. (4) The nosological classification of Parkinson's syndrome (based on clinical and morphological criteria) into 3 main groups, viz. postencephalitic, idiopathic and “arteriosclerotic”-senile, was supported by distinct, though not in all cases statistically significant, differences in the degree of disturbance of striatal DA metabolism. (5) In general, mild Parkinsonism, just manifest clinically, was associated with a disproportionately high degree of striatal DA deficiency. From this it was concluded that: (a) clinically manifest Parkinsonism represents the late, “decompensated”, stage of a disease characterized by a progressive striatal DA deficiency; and (b) the striatum can compensate functionally for lower degrees of DA deficiency. (6) Positive correlations could be established, within a certain range, between the severity of individual Parkinsonian symptoms (especially akinesia and tremor) and (a) the degree, and also the site, of the disturbance of DA metabolism within the nuclei of the basal ganglia; and (b) the sensitivity of the patients to levodopa's acute anti-akinesia effect. The latter observation was interpreted as suggesting that in Parkinsonism there exists a supersensitivity (probably of the “denervation type”) of striatal receptors to DA. (7) Based on the correlations, levodopa therapy can be regarded as a specific, though probably predominantly symptomatic, treatment of the main extrapyramidal symptoms of Parkinson's syndrome. (8) In Huntington's chorea the concentrations of DA and HVA in the putamen, pallidum and substantia nigra showed no significant deviation from control values; however in the caudate nucleus there was a small but statistically significant reduction in the levels of these compounds (9). The possible functional significance of the observed correlations for the pathophysiology of disorders of the basal ganglia such as the diseases of Parkinson and Huntington is discussed.