The ninth component of complement (C9) and the pore-forming protein (PFP or perforin) from cytotoxic T lymphocytes polymerize to tubular lesions having an internal diameter of 100 A and 160 A, respectively, when bound to lipid bilayers. Polymerized C9, assembled by slow spontaneous or rapid Zn2+-induced polymerization, and polyperforin, which is assembled only in the presence of Ca2+, constitute large aqueous pores that are stable, nonselective for solutes, and insensitive to changes of membrane potential. Monospecific polyclonal antibodies to purified C9 and PFP show cross-reactivity, suggesting structural homology between the two molecules. The structural and functional homologies between these two killer molecules imply an active role for pore formation during cell lysis.