Erythrocyte COMT activity was determined in 31 healthy persons (16 men, 15 women) and in 34 persons with endogenous depressive syndrome (12 men, 22 women). It was found that enzyme activity is significantly higher in healthy men than in healthy women. In the group of women with endogenous depressive syndrome COMT activity is elevated as compared with the group of healthy women (P less than 0.05). This is true of all forms of affective disease: bipolar, unipolar, and undifferentiated. High COMT activity in women with depression is apparent mainly in patients whose first and second degree relatives revealed psychiatric disturbances, particularly affective disorders. This supports the significance of the sex factor in the genetic transmission of affective disorders, and a possible involvement of COMT activity changes in the pathogenesis of such disorders in women. No correlation was found between the changes in COMT activity and the psychopathological picture of depression or the severity of endogenous depressive syndrome.