Cluster analyses were carried out on a sample of 100 depressed females. The study was based on the 14 items relevant to depressive phenomenology of the Structured Clinical Interview for DSM-III-R (SCID). Our findings support the existence of two classes, i.e., a vital (melancholic) vs. a nonvital cluster. The vital cluster is characterized by the following symptoms: a distinct quality of depressed mood, nonreactivity, early morning awakening, anorexia-weight loss, and cognitive and psychomotor disturbances. Patients belonging to the vital cluster exhibit disorders in the hypothalamic-pituitary-adrenal and thyroid axes and a markedly decreased availability of L-tryptophan to the brain. The vital depressives score significantly higher on the Hamilton Rating Scale for Depression as compared to those suffering from nonvital depression. The cluster-analytically derived class of vital depression and the DSM-III subtype of melancholia tend to be quite similar. Our findings support the isolation and the descriptive validity of a vital (melancholic) depressive syndrome.