This report describes the evaluation of 1,278 patients referred to The Johns Hopkins Hospital with dilated cardiomyopathy. After a careful history and physical examination, selected laboratory tests, and endomyocardial biopsy, a specific diagnosis was made in 49% of cases. In 16% of cases the biopsy demonstrated a specific histologic diagnosis. Myocarditis and coronary artery disease were the most frequent specific diagnoses; 51% of patients were classified as idiopathic. Thus a rigorous and systematic search can demonstrate an underlying cause for approximately one-half of patients with unexplained cardiomyopathy. Endomyocardial biopsy plays a crucial role in this evaluation. Six cases are presented which demonstrate the utility of endomyocardial biopsy in specific clinical situations. In addition to its routine use in monitoring rejection in heart transplant recipients, endomyocardial biopsy is indicated in the evaluation of possible infiltrative cardiomyopathy, in differentiating restrictive cardiomyopathy from constrictive pericarditis, and in diagnosing and monitoring doxorubicin cardiotoxicity. The importance of diagnosing myocarditis remains controversial, and disagreement persists about the utility of immunosuppressive therapy in these patients. A combination of clinical and histologic features can divide patients with myocarditis into 4 subgroups--acute, fulminant, chronic active, and chronic persistent. This classification provides prognostic information and may identify those patients who may respond to immunosuppression, as well as those likely to have adverse outcomes from such treatment. The continued development of novel molecular techniques may allow endomyocardial biopsy to provide greater prognostic and therapeutic information in the future.