Summary: Human γ-globulin causes a marked decrease in the C′1 and C′4 activity of guinea pig complement. This anticomplementary activity is enhanced by heating the γ-globulin at 56–60°C or by adsorbing it to bentonite. The inactivation of C′4 in serum occurs only in the presence of C′1. Following incubation with a source of C′1, a suspension of bentonite with adsorbed γ-globulin is capable of inactivating C′4 in serum fractions lacking C′1. This ability is abolished by the treatment of the suspension with diisopropyl-fluorophosphate. It is suggested that the reaction of γ-globulin with complement is similar to the first steps of complement fixation by an antigen-antibody complex.