Dilated cardiomyopathy is associated with various immunological abnormalities, such as decreases in the activity and subsets of suppressor T cells and in the activity of natural killer cells, suggesting the involvement of immunological mechanisms in the pathogenesis of this disease. I assayed several subsets and the activity of natural killer cells in the peripheral blood of 44 patients with diluted cardiomyopathy and compared the results with the clinical course. Compared with normal individuals, the patient group showed increases in cells positive for the subsets Leu 7 and Leu 11. Double staining method revealed that natural killer cell groups were positive for Leu 7, Leu 11 and Leu 15 but negative for Leu 2a. The activity of natural killer cells was decreased in all cases, particularly in the subgroup with mild illness. Addition of interleukin 2 (IL-2) caused no increase in activity in any of the cases. Compared with the mild subgroup, the subgroup with severe illness included more male patients and had a shorter clinical course (p less than 0.05). Of the 43 patients who underwent gallium 67 (Ga-67) myocardial scintigraphy, four demonstrated an accumulation of the contrast material in the myocardium, and all of whom belonged to the mild subgroup. These results suggest that inhibition of the function or activation of natural killer cells and the pathophysiology of chronic myocarditis are intimately associated with the occurrence of at least the mild form of dilated cardiomyopathy.