SummaryTwo entry mechanisms of HIV occur in both lymphocytes and macrophages incubated with purified virus suspensions: (a) direct fusion of the viral envelope with the cell membrane and (b) receptor-mediated endocytosis via clathrin-coated pits and vesicles. Both mechanisms are shown in detail in a time-interval series of electron micrographs. The two lipid bilayers of the viral envelope and of the cellular membrane usually fuse seamlessly within 1–3 min at 37°, but occasionally membrane ruptures occur, leading to rapid cytopathic effects, i.e., vacuolization and cytolysis only a few minutes later. In the course of virus-cell fusion, gp 120 is integrated into the cell membrane; subsequent syncytia formation was observed after 1 h of incubation. The core disintegrates and releases the viral ribonucleoprotein through the opening at the fusion site into the cytoplasm.