The sequence of morphological changes following the interactions between macrophages of nonimmunized rats and allogeneic liver cells in vitro were examined by scanning and transmission electron microscopy. The effector cells could be identified as macrophages because of their morphologic characteristics and their ability of latex beads incorporation. The cytotoxic reactions required close contracts between the reactive cells. Effector membrane processes and microvilli attached the target cell surface. Broad contacts and, more frequent, point contacts were observed. After 4 to 5 hrs of incubation the target cells showed pinocytotic activities in the contact regions. Later on submembraneous cytoplasmatic leaks or defects indicated the increasing damage of the target cells. Finally, liver cell ghosts with degenerated organelles were found as morphologic expression of general target cell destruction whereas effector macrophages did not show any damage during the cytotoxic reaction.