Studies on erythrocytes have shown that the formation of the membrane attack complex on a cell surface inevitably results in lysis. However, it is known that nucleated cells are much more difficult to kill with complement^1–3, although the molecular basis of this resistance has never been established. We have shown that a very early intracellular event, occurring within seconds of formation of the attack complex in the membrane, is a rise in cytoplasmic Ca²⁺ (ref. 4), which can activate cell responses without cell death^5,6. Here we report the use of a monoclonal antibody to the terminal complement component C9 (refs 7, 8, 13), quantified by ¹²⁵I and visualized by fluorescein, to demonstrate a protection mechanism in polymorphonuclear leukocytes (PMNs) attacked by complement, involving removal of the attack complex by vesiculation. Concomitantly, there is a Ca²⁺-dependent activation of reactive oxygen metabolite production without cell lysis. These findings have important implications in the evolutionary and pathological significance of the terminal components of the complement pathway.