The diagnosis and etiology of myocarditis and perimyocarditis are often difficult to ascertain. We therefore investigated regulator and humoral and cellular effector mechanisms in patients with viral heart disease (Coxsackie B3, influenza, EBV, mumps). In acute carditis, OKIA1-positive cells were increased and no significant alteration in suppressor cell activity was observed in our patients in contrast to others reports. The characteristic immunofluorescent pattern is the presence of antimyolemmal antibodies (AMLA) with rat and human collagenase-pretreated intact cardiocytes (in titers of 1:40-1:320) as antigens. The pattern is indistinguishable on cardiocytes from antibodies against cytoskeletal antigens (microtubules, intermediate filaments--tubulin/vemitin) when associated with antibodies directed against the Z-bands. In contrast, only anti-interfibrillary antibodies are present in cytomegalovirus myocarditis. The antimyolemmal fluorescence can be absorbed with the respective causative virus, indicating that the antibodies are cross-reactive. AMLA-positive sera induce cytolysis of vital rat cardiocytes in vitro, indicating that the antibodies are of pathogenetic relevance. Cytolytic serum activity could be absorbed out with the respective virus. Immunohistologic specimens obtained from patients with carditis demonstrate the fixation of IgG-type antibodies to the sarcolemma that also fix complement. In the acute phase of carditis, circulating immune complexes were also measured, thus monitoring immunoreactivity. Cellular effector mechanisms against vital cardiocytes were maintained or even slightly enhanced; in vitro NK-cell activity against K 562, however, was decreased. This is compatible with a more target-specific cytotoxicity in carditis but reduced NK-cell activity in peripheral blood cells.