Qualitative electron microscopy was performed to verify whether brain pathology in schizophrenia and bipolar disorder is associated with alterations of oligodendroglial cells and myelinated fibers. Ultrastructural signs of apoptosis and necrosis of oligodendroglial cells were found in the prefrontal area 10 and the caudate nucleus in both schizophrenia and bipolar disorder. Damage of myelin sheath lamellae, with the formation of concentric lamellar bodies, were detected in both brain structures in schizophrenia. There was also a significant decrease in the area of the nucleus and the volume density of mitochondria in oligodendrogliocytes in the caudate nucleus and in the prefrontal cortex in schizophrenia, as compared to normal controls. Volume density of heterochromatin was significantly increased (+14%) in the caudate nucleus in schizophrenia. The density of concentric lamellar bodies (as an indicator of damage of myelinated fibers) was dramatically increased (4.5-fold) in the caudate nucleus in schizophrenia, as compared to controls, and was positively correlated with volume density of heterochromatin. Multiple regression analysis and analysis of covariance demonstrated that these changes could not be explained by the effects of postmortem delay, age, neuroleptic medication, or gender. Pathology of oligodendroglia might be an essential feature of severe mental disorders.