Experiments using the selective divalent cation chelator, ethylene glycol tetraacetic acid (EGTA) showed that the alternate complement pathway was involved in the bactericidal action of bovine serum on two strains of E. coli. The bactericidal system was shown, in experiments involving EGTA and epsilon-amino caproic acid, to be independent of Ca++ and the C1 unit of complement. The fixation of the complement components C3-C9 by endotoxin does not require a functional classical pathway ((C1, C4 and C2). In the case of one coliform strain (W1) however, there was an almost total dependence on a factor absorbable at 0 degrees with homologous bacteria, and which appeared to be a natural antibody. These results suggest that in certain circumstances in the cow, gamma globulins may be directly involved in the activation of the alternate complement pathway.