The purpose of this investigation is to determine if the high prevalence rates of major depression, panic disorder, and agoraphobia found in tertiary-care studies of irritable bowel syndrome and medically unexplained gastrointestinal symptoms are also found in the general population. Structured psychiatric interviews on 18,571 subjects from the NIMH Epidemiologic Catchment Area (ECA) Study were reviewed for prevalence of gastrointestinal distress symptoms and selected psychiatric disorders. Medically unexplained gastrointestinal symptoms had a high prevalence in the general population (6-25%). When compared with those reporting no gastrointestinal symptoms, subjects who report at least one of these symptoms were significantly more likely to have also experienced lifetime episodes of major depression (7.5% vs 2.9%), panic disorder (2.5% vs 0.7%), or agoraphobia (10.0% vs 3.6%). Subjects with two gastrointestinal symptoms had even higher lifetime rates of depression (13.4%), panic (5.2%), or agoraphobia (17.8%). Lifetime rates of affective and anxiety disorders in the general population are higher in subjects with gastrointestinal symptoms compared with subjects without gastrointestinal symptoms. An even higher prevalence of affective and anxiety disorders is found in patients with medically unexplained gastrointestinal symptoms in tertiary-care clinics. Future studies are needed in primary-care populations where prevalence rates of psychiatric illness are probably intermediate between those of the general population and tertiary care.