Cell-mediated muscle fiber injury occurs in inclusion body myositis (IBM), polymyositis (PM), and even in Duchenne dystrophy (DD). Most of the autoaggressive cells are T cells and macrophages, but some are killer/natural killer (K/NK) cells. We here compare the frequencies per 1,000 muscle fibers of endomysial K/NK cells of varying cytotoxicity with those of T cells and macrophages in 8 cases each of IBM, PM, and DD. Two-micrometer serial cryostat sections were analyzed. The Leu-4 marker, present on all T cells and some K/NK cells, and the Leu-7 and Leu-11 markers, present on K/NK cells, were localized by paired immunofluorescence. Macrophages were demonstrated by the acid phosphatase reaction. In IBM, PM and DD, the respective average cell counts per 1,000 muscle fibers were: Leu-4+7- cells (T cells not expressing a K/NK marker)--710, 530, and 59; Leu-4+7+ cells (K/NK cells of low K/NK cytotoxicity)--294, 163, and 13; Leu-4-7+ cells (K/NK cells of intermediate cytotoxicity)--32, 10, and 2; and macrophages--292, 251, and 38. Leu-11+ K/NK cells that have the highest killing activity were virtually absent in all cases. The data suggest a limited role for antigen and major histocompatibility complex unrestricted K/NK cells, as compared with antigen-specific and major histocompatibility complex-restricted T cells, in IBM and PM. Further, the findings cast doubt on the significance of either T cells or K/NK cells in mature muscle in DD.(ABSTRACT TRUNCATED AT 250 WORDS)