We have previously obtained light microscopical immunocytochemical evidence for cell-mediated muscle fiber injury and destruction in polymyositis and inclusion body myositis. To evaluate further interactions of the different cell phenotypes with each other and with the muscle fibers, the T8, T4, and Leu 7 markers in 7 cases of polymyositis and in 9 cases of inclusion body myositis were localized by immunoelectron microscopy. In the early stages of the cell-mediated process, T8+ cells and macrophages are apposed against, and/or send spikelike processes into, nonnecrotic muscle fibers. Leu-7+ cells penetrate fibers infrequently, and T4+ cells do not penetrate muscle fibers. Subsequently, an increasing number of T8+ cells and macrophages traverse the basal lamina; focally replace, displace, or compress the fiber; and spikes from these cells honeycomb the adjacent muscle fiber regions. The macrophages contain only few heterophagic vacuoles and therefore act in a cytotoxic rather than a phagocytic capacity. The integrity of the muscle fiber surface membrane facing the invading cells is maintained, but the possibility also exists that the membrane is damaged and rapidly repaired, or that the damage cannot be detected by electron microscopy. Nearby fiber regions often show either degenerative or regenerative changes. Ultimately, segments of the entire muscle fiber are replaced by the invading cells.