• To examine the feasibility of using antidepressant medication to treat major depressive syndromes in the hospitalized medically ill, we reviewed a series of psychiatric consultations meeting the following criteria: (1) the consultant diagnosed a major depressive syndrome, (2) treatment with an antidepressant was advised, (3) the consultee initiated the antidepressant, and (4) hospitalization had been prompted by a major medical illness. The final sample of 50 consultations, representing less than 5% of the cases reviewed, was assessed by retrospective study of entries in the medical record. Judgments regarding response were thus a function of routine clinical observation and care. Drugs were not randomly assigned; rather, the choices represented ongoing clinical usage patterns. Two major points emerge from the data of the study. First, 32% of the trials were terminated due to side effects judged to be unacceptable by the physicians or consultants. Delirium accounted for half of such side effects; cardiotoxicity, however, was not evident. Second, only 40% of patients with medical illnesses, including malignant neoplasm, insulin-dependent diabetes, and epilepsy, responded to treatment. The trials of antidepressants in medical-surgical inpatients did not achieve the pattern of therapeutic responses routinely characterizing comparable interventions in psychiatric patients with primary affective disorder.