Peripheral blood leukocytes from 14 patients with idiopathic dilated cardiomyopathy (IDC), 13 patients with ischemic congestive heart failure, and 12 controls were characterized using different antibodies. The proportions of B lymphocytes, T lymphocytes, and the different T lymphocyte subsets were estimated. No difference between the three groups could be found in the various T and B cells subpopulations. Using a two-color direct immunofluorescence technique, the occurrence of circulating T helper/inducer (Leu-3a) and T cytotoxic/suppressor cells (Leu-2a) expressing HLA-DR antigens was examined. Only IDC patients demonstrated increased levels of HLA-DR-positive T helper/inducer cells (2.8 ± 2.4%) and T cytotoxic/suppressor cells (2.8 ± 2.3%) as compared with patients with ischemic congestive heart failure (0.8 ± 0.7 and 1.0 ± 1.0%, respectively) and controls (0.6 ± 0.5 and 0.9 ± 0.6%, respectively). When individual IDC patients were studied, 4 out of 12 patients had an increased level of HLA-DR-expressing T helper/inducer cells, and 7 out of 12 patients had elevated HLA-DR-positive T cytotoxic/suppressor cells. The findings suggest that activation of the T lymphocytes may be of importance in the pathogenesis of IDC.