The first 100 consecutive patients to undergo right ventricular endomyocardial biopsy at the Mayo Clinic were divided retrospectively into five groups, depending on the prebiopsy clinical diagnosis, and the biopsies were review histologically in a single-blind format. Group 1 consisted of 34 patients with a diagnosis of unexplained congestive heart failure and a dilated heart; of these, 4 (12%) had active myocarditis by biopsy. Of the six patients in group 2 with a clinical diagnosis of myocarditis, only one (17%) had biopsy evidence of inflammation, but two (33%) had changes that, in the clinical setting, were suggestive of cardiomyopathy. Group 3 consisted of 27 patients with dysrhythmia, syncope, or cardiac arrest but without congestive heart failure; of these, 4 (15%) had active myocarditis by biopsy, and 8 (30%) had changes that, with the clinical history, were consistent with cardiomyopathy. Group 4 included 19 patients with unexplained congestive heart failure and a nondilated heart; 4 (21%) had cardiac amyloid on biopsy. Group 5 was a diverse group of 14 patients with possible cardiac involvement by a known systemic disease; myocardial disease was documented by biopsy in 7 (50%). On the basis of these findings, we recommend endomyocardial biopsy (1) in patients with dilated cardiomyopathy in whom myocarditis is suspected, (2) in patients with the clinical diagnosis of active myocarditis in whom tissue documentation is indicated before treatment with anti-inflammatory or immunosuppressive drugs, (3) in patients with clinically unexplained life-threatening dysrhythmias in whom myocarditis or cardiomyopathy may be present, and (4) in patients with apparent hypertrophic or restrictive cardiomyopathy in whom cardiac amyloid may be present.