The diagnosis, pathogenesis and etiology of myocarditis are often difficult to establish with certainty. Consequently, we investigated cellular regulator and effector mechanisms in patients with viral heart disease (Coxsackie B3, influenza, EBV, mumps) as well as other inflammatory heart diseases which could not be classified etiologically. In acute myocarditis there was an elevation of B-and activated T-lymphocytes (OKIa 1-positive) but, in contrast, no significant changes in the activity of peripheral suppressor T-cells (OKT 8-positive). The activity of cell-specific lymphocytic effector mechanisms against vital cardiocytes was unchanged or slightly elevated in myocarditis, while the activity of the less target cell specific natural killer cells, which were measured in vitro against K562 tumor cells, was diminished. These findings are indicative of increased activity of target specific cytotoxic effector mechanisms and a reduction in the activity of nonspecific cellular effector mechanisms in peripheral blood.