Human cells in tissue culture were found to acquire a new membrane antigen detectable by natural antibody in human serum. Subsequent experiments showed that the antigen originated from fetal calf serum used in the tissue culture medium, and that it was not γ-globulin in the bovine serum. Cultured cells from sarcomas, embryos, and melanomas contained higher concentrations of the antigen than those from carcinomas and normal tissues. Human sera from both cancer patients and normal donors contain natural antibody to this antigen. Therefore, this antigen may introduce artifacts in tumor immunology studies in which human sera are tested for serologic reactions against human cells cultured in bovine sera.