Patients with major depression admitted to hospital with acute stroke (n = 44), acute myocardial infarction (n = 25), or acute spinal cord injury (n = 12) were examined for differences in their phenomenological presentation of major depression. Depressed stroke patients were found to have significantly higher scores on the syndrome clusters for generalized anxiety and ideas of reference than depressed cardiac or spinal cord injury patients. In addition, significantly more stroke patients met diagnostic criteria for generalized anxiety disorder compared with the other two groups. Although spinal cord injury patients were younger, more likely to be treated with benzodiazepines, and less likely to be treated with beta-blockers, none of these factors distinguished stroke patients with anxious depression from stroke patients with depression only. These findings are consistent with the hypothesis that the etiology of depression following stroke may be different from that associated with myocardial infarction or spinal cord injury.