The authors conducted a clinical trial to examine the efficacy and safety of nortriptyline in the treatment of major depression in elderly medical inpatients. The diagnosis of major depression was made by a psychiatrist in 41 of 680 patients 65 years of age or older. The study was balted at the midpoint because of inadequate patient recruitment, primarily a consequence of medical illnesses that prevented more than 80% of eligible patients from participating in or completing the clinical trial. Major or minor medical contraindications to the use of antidepressants were present in over 90% of depressed patients. Short-term follow-up was conducted on untreated depressed patients, those receiving antidepressants at the time of assessment, and those in whom antidepressant treatment was initiated after assessment. Non-randomized exposure to antidepressants did not predict remission of depression at follow-up due to spontaneous remission in the untreated group. Given the prevalence of medical contraindications to antidepressant use among depressed elderly patients and the problems with side effects in treated patients, there were few depressed, elderly hospitalized patients who were candidates for antidepressant therapy.