The precise mechanisms and tissue sites involved in the in vivo detoxification of endotoxin remain unresolved. Although a number of studies have indicated that circulating plasma is a principal site of endotoxin inactivation (1–3), it was believed that the complement system was not required for detoxification of endotoxin (1). However, a recent report which demonstrated the increased susceptibility of C6 deficient rabbits to the injection of bacterial endotoxin suggests that complement may be important (4). Endotoxin can activate the complement system either by the classical mechanism proceeding through the activation of C1, C4 and C2 to activate C3, or via the alternate or bypass pathway proceeding through another series of proteins, as yet incompletely defined, to enter the complement sequence directly at the C3 step (5–7). In this study a further attempt is made to evaluate the role of complement in the detoxification of endotoxin, with particular reference to the contribution of the early (C1, C4 and C2) and late acting (C3–C9) complement components.