The present study investigates the clinical significance of several possible causative or conditioning factors which have been proposed to be involved in the pathogenesis of dilated cardiomyopathy (DCM). By reviewing the medical records of 68 patients with DCM, we found a definite, and suggestive family history in 16%, and 28%, respectively, and antecedent flu-like symptoms in 43%. A history of hypertension was observed in 35%, habitual alcoholism in 49% and diabetic pattern on glucose tolerance test in 37%. We then classified the study patients into three groups; familial, myocarditic and acquired groups. The familial group showed advanced myocardial damage with the poorest prognosis. Abnormal T-cell subsets in this group suggested that genetically determined abnormal immune response is involved in the development of DCM. In the myocarditic group, endomyocardial biopsy demonstrated mononuclear cell infiltration in 53% and the myocardial damage and prognosis were of intermediate severity. The acquired group showed significantly more frequent histories of hypertension, habitual alcoholism or diabetes than their age- and sex-matched controls, suggesting that they developed the disease in association with these factors. The severity of hemodynamic impairment and myocardial damage was the least extensive and prognosis was relatively favorable in this group. These different clinical features in the three groups may provide evidence that these factors actually contribute to the development of myocardial damage in DCM and that the condition is a clinical syndrome associated with heterogeneous etiologies or conditioning factors. Determination and management of these factors would be of practical value in treating patients with DCM that has no established therapy against underlying etiologies.