Echogenicity of the brainstem raphe was assessed in patients with major depression, bipolar affective disorders, and schizophrenia and compared with healthy adults employing transcranial color-coded real-time sonography. Forty probands were enrolled in each group. A highly significant reduction in raphe echogenicity was detected only in patients suffering from major depression. Echogenicity of the raphe was independent of age or sex and did not correlate with severity of the depressive syndrome or patient state. These findings are suggestive of structural desintegration of the brainstem raphe in unipolar depression, an anatomical region assumed to be a biological focus in the pathogenesis of depressive syndromes.