When the plasma membrane of eukaryotic cells is mechanically injured, Ca 2+ influx triggers a rapid repair process that involves exocytosis (Reddy et al., 2001; McNeil, 2002; McNeil et al., 2003). Although the precise repair mechanism is still unknown, current hypotheses propose that resealing is directly mediated by the delivery of intracellular membrane to the cell surface. These models suggest that Ca 2+-dependent exocytosis acts by providing a membrane patch (McNeil et al., 2000) or by relieving plasma membrane tension, which facilitates resealing (Togo et al., 2000). However, such models cannot explain the process by which cells repair the stable protein-lined transmembrane lesions caused by pore-forming proteins (Campbell and Morgan, 1985; Browne et al., 1999; Walev et al., 2001; Keefe et al., 2005). Experiments using the complement membrane attack complex (Morgan and Campbell, 1985) or the bacterial toxin streptolysin O (SLO; Walev et al., 2001) found that membrane resealing after pore formation is also Ca 2+ dependent. Despite this common requirement, until now, the repair of transmembrane pores was largely viewed as a process distinct from the resealing of mechanical wounds and was assumed to involve considerably longer periods of time. In this study, we show that SLO-permeabilized cells reseal with the same fast kinetics previously reported for the repair of mechanical wounds (Steinhardt et al., 1994; Reddy et al., 2001) and demonstrate that both processes involve a rapid form of Ca 2+-dependent endocytosis.