The distribution of serum heterocytotoxicity mediated by natural antibody activation of the classical complement pathway and by antibody-independent activation of the alternative complement pathway in serum samples obtained from normal neonates and adults and cancer patients was investigated employing a metabolic inhibition (MI) assay. Levels of MI activity were significantly (p less than .01) higher in female cancer patients and in women taking oral contraceptives in comparison with controls. MI activity in neonates was approximately 50% of average adult levels. Maximal activity was observed in patients with visceral cancer, particularly those with anenocarcinoma. MI activity was significantly (p less than .05) less in subjects with sarcomas than in patients with adenocarcinomas. The results suggest that the MI assay may be useful in measuring natural antibodies and activation of the alternate complement pathway which represents the mechanisms of natural immunity against tumors.