The surfaces of activators of the alternative pathway, such as zymosan and rabbit erythrocytes, provide sites which protect bound C3b from inactivation by C3b inactivator (C3bINA) and β1H, and P,C3b,Bb from decay-dissociation by β1H. This circumstance permits surface-associated amplified generation and deposition of C3b. The capacity of a bacterial surface, if analogous to zymosan and rabbit erythrocytes, to protect and thereby accumulate increasing amounts of C3b by local circumvention of the regulatory proteins would be compatible with a unique role of the alternative pathway in host defense. The susceptibility of C3b bound to Escherichia coli to C3bINA was compared with that of C3b bound to the nonactivator, sheep erythrocytes, in the state, EAC4b,3b. E. coli W3110, killed by heating at 60°C for 60 min, activated the alternative pathway in human serum diluted 1:5 in GVB containing 2 mM Mg++ and 8 mM EGTA as demonstrated by 82% C3 and 87% B consumption.