The purpose of this study was to determine the nature and extent of comorbidity among patients with DSM-III-R hypochondriasis and to examine the relationships between this disorder and coexisting psychiatric illness. For this purpose, patients seen in a general medicine clinic were screened using measures of hypochondriacal attitudes and somatic symptoms. Those scoring above an established cutoff were given a structured diagnostic interview. In this manner, 50 patients who met DSM-III-R criteria for hypochondriasis and 50 age- and sex-matched controls were identified. The presence of other psychiatric disorders (current and past) was determined by means of the same diagnostic interview. More hypochondriacal subjects (62.0%) had lifetime comorbidity than did controls (30.0%). Major depression, the most frequent comorbid disturbance, was usually current and most often had an onset after that of hypochondriasis. Panic disorder with agoraphobia, the most frequent anxiety disorder, was also current but often began before or at the same time as hypochondriasis. Few subjects met criteria for somatization disorder but a third qualified for a subsyndromal form of this disorder. The data show that, in medical outpatients with hypochondriasis, mood and anxiety disorders frequently coexist. This comorbidity is subject to varying interpretations including overlap of symptom criteria, treatment-seeking bias, and the possibility that hypochondriasis predisposes to or causes the comorbid disorder, as seems likely in the case of depression. In some instances hypochondriasis may be an associated feature of another illness.