The sera from patients with primary heart and skeletal muscle diseases, hospitalized patients without intrinsic muscle disease from an area endemic for Trypanosoma cruzi infections, and normal subjects (N = 693) were studied for the presence of immunoglobulin G (IgG) antisarcolemma activity using serologic methods. The prevalence of elevated serum IgG antisarcolemma activity from patients with chronic Chagas' cardiomyopathy, idiopathic cardiomyopathy, polymyositis, and Duchenne muscular dystrophy was 58.9 +/- 10.4% (N = 101) (P less than 0.001 when compared to normal subjects). Two of twelve (16.7%) patients with acute T. cruzi infection and parasitemia developed elevated antisarcolemma titers, and 9/46 (19.6%) patients with chronic T. cruzi infection without evidence of cardiomyopathy yielded high antisarcolemma titers. On the other hand, patients with chronic T. cruzi infection with advanced cardiomyopathy yielded high antisarcolemma titers in 35/74 (47.3%) (P less than 0.001 when compared to normal subjects). Radioimmunoprecipitation showed a circulating antibody to a 25-kDa T. cruzi polypeptide (P25) in 16/17 (94.1%) patients with advanced cardiomyopathy and T. cruzi infection. No such antibody was shown in 12 asymptomatic subjects with chronic T. cruzi infection.