Thirty-five consecutive patients with Cushing's syndrome were studied prospectively prior to treatment. A consistent constellation of psychiatric disturbances was found, including impairments in affect (depressed mood and crying), cognitive functions (decreased concentration and memory), and vegetative functions (decreased libido and insomnia). A statistically significant relationship was found between the overall psychiatric disability rating and cortisol and ACTH level. The relationship of depressed mood and hormone levels was examined. Low ACTH levels were significantly associated with milder rather than pronounced depressed mood. The implications of the similarities in psychiatric manifestations between Cushing's syndrome and the primary affective disorders are discussed.