OBJECTIVE To examine and compare the profile of cognitive symptoms, somatic symptoms, and somatic complaints in younger and older medical inpatients diagnosed with major depressive disorder (MDD). METHODS Cross-sectional cohort. METHODS Male patients aged 20-39 years (n = 116) and aged 70-102 years (n = 332), consecutively admitted to the medical and neurological services of a VA medical center, underwent psychiatric evaluations for depression. METHODS Depressive symptoms were measured using the observer-rated Hamilton Depression Scale and the self-rated Geriatric Depression Scale using an "inclusive" approach (symptoms rated regardless of etiology). Data on 12 common somatic complaints were also collected. Clinical diagnoses of MDD were made by a psychiatrist based on the Diagnostic Interview Schedule and other psychiatric and physical health data. RESULTS After controlling for severity of medical illness, functional status, and alcohol use, symptoms that discriminated MDD best among younger men were loss of interest, feelings of guilt or of being a burden, suicidal thoughts, and depressed mood (primarily cognitive and affective symptoms). Among older men, loss of interest, insomnia, suicidal thoughts, and hypochondriasis most strongly differentiated depressed from non-depressed patients (mixture of cognitive and somatic symptoms); fatigue, weight loss, genital symptoms, and somatic anxiety were weakly related or unrelated to MDD. Number of somatic complaints (headache, dizziness, palpitations, etc.) helped differentiate patients with MDD; although equally common among depressed young and older patients, a distinct pattern of complaints emerged in each age group. CONCLUSIONS Cognitive symptoms of depression can help to distinguish medical inpatients with and without MDD. In older adults, however, somatic symptoms cannot be ignored and may be more important for diagnosing MDD than previously realized. These findings will help clinicians identify patients with MDD and differentiate them from non-depressed patients with medical illness.