The records of 172 depressed inpatients were examined retrospectively to determine the presenting symptoms, history of stress, clinical course, and personality features characteristic of patients whose depressive syndrome had become autonomous. The autonomous distinction was based on observation of a lack of responsiveness of the syndrome to environmental events during the first week of hospitalization prior to drug treatment. The autonomous criterion was selected since it is a central characteristic of recent psychobiological models of depression and it could be operationally defined, reliably rated, and assessed independently of other patient characteristics. Sixty-eight autonomous patients were identified and compared with 104 patients who were responsive to hospitalization. The characteristics of the autonomous patients are discussed in relation to the previous literature, other diagnostic systems, and the criteria proposed for the diagnosis of melancholia in DSM-III