Atopic sera were shown to be defective in serum bactericidal activity by a reaction dependent upon the integrity of the alternative pathway of complement activation. In normal human sera, the efficiency of such a reaction could be modulated by the addition of thermostable serum fractions with inhibitory and stimulatory activity, as demonstrated on two different assay systems. Atopic sera contained the inhibitory activities, but no stimulatory activity. The bactericidal defect of atopic sera was shown to be familial, but its hereditary mechanism could not be unambiguously interpreted.