From 1975 to 1985 at the Massachusetts General Hospital, 245 biopsies were performed in 170 patients to rule out clinically suspected myocarditis or for follow-up study of previously diagnosed myocarditis. Direct and indirect immunofluorescence studies were conducted on 193 specimens. Three-fourths of the biopsies did not show evidence of myocarditis. Endomyocardial biopsy specimens from patients with active myocarditis most frequently contained C3 whereas serum samples from patients with resolving myocarditis most often contained antimyocardial antibodies. In general, immunological findings correlated closely with the status of disease activity in these patients, including four who had had multiple relapses and immunosuppressive therapy. Our study confirms the presence of a humoral immunological mechanism, either primary or secondary, in myocarditis and indicates that immunological studies are a valuable adjunct to morphological examination.