We investigated the nosology of endogenous depression by numerical taxonomy. Five hundred and sixty-nine patients diagnosed as having unipolar major depressive disorder in the NIMH Clinical Research Branch Program on the Psychobiology of Depression — Clinical were studied. Thirty-six symptoms which might distinguish endogenous from non-endogenous depressions were chosen from the literature. Patients' symptom profiles assessed by structured interview were grouped by two methods: a K-means improvement of Ward's method of cluster analysis, and a latent class algorithm. The methods produced very similar groups and several internal validity criteria suggested that the groups were not spurious. Cluster 1, ‘nuclear depression,’ included a nucleus of patients common to multiple definitions of endogenous depression. The non-nuclear group scored as less neurotic than the nuclear group on personality tests administered during the index episode. The groups do not differ in frequency, number or severity of reported life events prior to onset of the index episode. The nuclear group shows a poor prognosis on two-year prospective follow-up, greater disturbance on personality inventories, and increased heritability of depression in siblings.