Human sera from healthy individuals have been shown to react with viral antigens in preparations of de-tergent-disrupted C type viruses from monkeys. In this report, it is demonstrated that (populations of) these human antibodies react with highly purified envelope glycoproteins of the simian sarcoma virus-simian sarcoma-associated virus complex and the Friend leukemia virus complex. Several immunological parameters influencing human antibody binding to C type tumor virus antigens have been characterized. These parameters indicate that human antibodies tend to bind to what is probably a subset of the antigenic determinants on the virus envelope antigens and that different human sera recognize the same antigenic determinants on the virus envelope antigens tested. The possible origin of these antibodies is discussed. Evidence for the presence of oncornavirus particles (1-13) as well as viral antigens (14-20), RNA-dependent DNA polymerase (reverse transcriptase) (21-25), and nucleic acids (22,(26)(27)(28)(29) in normal and malignant human tissues has accumulated steadily over the past few years. Another approach to search for C type virus information in humans is to screen sera from healthy individuals and from patients for antibodies reacting with tumor virus antigens. The presence of such antibodies may indicate previous viral infection.In the absence of C type tumor virus strains of undisputable human origin, we made use of the observation that comparative analysis of C type animal viruses generally revealed close immunological and biochemical similarities between virus strains isolated from the same or evolutionary related species. It could, therefore, be assumed that the yet putative human C type viruses may share antigenic determinants and nucleic acid homologies with virus strains of higher primates-i.e., monkeys and apes. For this reason we have used structural proteins of C type viruses from monkeys to survey human sera for the presence of antibodies reacting with C type viral antigens.Our previous investigations revealed the presence of antibodies in the majority of human sera that react with antigens in preparations of C type primate viruses (30-3). These data are in agreement with related findings from some laboratories (34-36), but contradict reports from several others that were unable to demonstrate human antibodies reacting with RNA tumor virus antigens (37-39). The reasons for these discrepancies remain unclear at present, but they may have been caused by using different human sera, different immunological detection techniques, virus antigens prepared by different procedures, and different interpretation of the data (discussed in refs. 30 and 31).To resolve these discrepancies, both improvement of the immunological detection techniques and the use of viral antigens purified to homogeneity (40, 41) seemed imperative.This publication deals with the presence of antibodies inThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby...