Light microscopic and morphometric studies were performed on brain stem lesions in 8 patients with Pick's disease. Neuronal loss and gliosis were observed in the red nucleus, substantia nigra, and the nucleus of locus ceruleus, but its degree was slight or moderate. Argyrophilic inclusions were observed in 4 patients, strongly argyrophilic in 2 of them and slightly argyrophilic in the other 2. Demyelination was noted in the fronto-pontine tract of the cerebral peduncle in 5 patients, and degeneration was observed in the longitudinal pontine fascicules. Measurements of the specimens showed a smaller brain stem, midbrain, and the pons in the patients with Pick's disease than in the control group ; the difference was the most marked in the midbrain followed by the pons. The medulla oblongata did not differ between the two groups. Both tegmentum and the base were smaller in the midbrain, and the base was smaller in the pons. However, the area/brain weight did not differ between the two groups. The substantia nigra showed a reduction in number of cells and area in the patient group than in the control group. Cells containing melanin were significantly decreased on all the medial, central, and the lateral sides, but the number of cells not containing melanin was similar between the two groups. The decrease in area was more marked. Therefore, the cell density was higher in the patient group. Thus, in the patients with Pick's disease, degeneration was observed at various sites of the brain stem. Some of the changes were secondary to damage to the cerebrum and basal ganglia, but others were primary lesions.