C3 inactivator was undetectable in the serum of a previously described patient with increased susceptibility to infection, hypercatabolism of C3 and multiple protein deficiencies. His red cells were positive with specific C3-Coombs reagent but became negative after infusion of normal plasma. Incubation of his red cells with normal serum or with purified C3 inactivator rendered them C3-Coombs negative, whereas incubation in his own serum or buffer did not alter the C3-Coombs positivity. C3 deposited on red cells in vitro by treatment of purified C3 with trypsin or with C1s, C4 and C2 became similarly unreactive with C3-Coombs reagent following incubation with C3 inactivator. C3 inactivator, in addition to its effect on cell-bound C3, acted on fluid phase C3b to yield a product of approximately unchanged molecular size but with an electrophoretic mobility similar to that of C3c. C3 inactivator may play a role in conversion of C3b to C3c in vitro and, perhaps, in vitro.