Interest in the long-neglected neuropathology of major affective disorders has recently been rekindled, partly because of the emergence of brain-imaging techniques. We review the literature suggesting that attention be given to the neuroanatomy and neuropathology of primary and secondary affective disorders. Computerised tomography studies show that patients with affective disorders tend to be similar to schizophrenic patients and significantly different from normal control subjects in ventricle:brain ratio, sulcal widening, and cerebellar vermian atrophy. As yet, there are few neuropathological investigations of the brains of patients with primary affective disorders. Suggestions for further research in the neuropathology of affective disorders are offered.