Antibodies to a synthetic undecapeptide (NH2-Cys-Glu-Asn-Pro-Ser-Gln-Phe-Tyr-Glu-Arg-Leu-COOH), the sequence (except cysteine) of which was deduced from a previously reported cloned human retroviral gag-generelated DNA sequence ern-1, were raised in rabbits. In immunohistochemical staining these antibodies reacted with normal human first-trimester placentas and with blighted ova and benign and malignant trophoblastic tumors (hydatidiform and destructive moles, choriocarcinomas) but not with any other normal embryonic or adult tissues tested. In all tissues the reactivity was mainly confined to cells with trophoblastic morphology. In immunoblotting the antibody detected an Mr 75,000 polypeptide in syncytiotrophoblasts isolated from first-trimester placentas and in three different lines of cultured choriocarcinoma cells. The undecapeptide blocked the reactivity of the antibody.In a previous study (13) using the feline endogenous retrovirus RD114 and antibodies to its major structural protein p30 as reagents, we demonstrated p30-related antigen in human placental syncytiotrophoblasts. Further, a study (13) of 1540 human cord blood sera revealed the presence of RD114 p30-reactive antibodies in 118 (7.7%) sera. Antibodies to synthetic peptides, which were based on MuLV p30 amino acid sequences or sequences of env genes, have been found to be reactive with the native structural proteins of murine retroviruses (14). In the present study we used antibodies to an undecapeptide, which has partial sequence homology to MuLV and BaEV p30 proteins. The undecapeptide sequence was inferred from the nucleotide sequence of the human proviral locus, erv-1 (7). This antibody detects a polypeptide antigen in syncytiotrophoblastic cells of human placentas both in vivo and in culture. Type C endogenous retroviruses are widespread in birds and mammals. They have also been recovered from several primates, including the Old World monkeys, baboon, stump-tail macaque, rhesus, and colobus, and the New World owl monkeys. The major source for isolation of endogenous retrovirus from baboons is the placenta (see ref. 1 for review). In humans, particles resembling type C or type D retroviruses have been seen budding from the syncytiotrophoblast layer of placentas (2, 3) and from cultured teratocarcinoma cells (4). In addition, small retrovirus-like particles have been seen in some human oocytes (5). Human endogenous retroviruses have not been isolated in an infectious form and producer cell lines have not been established.Evidence has been presented that human DNA contains retrovirus-related nucleotide sequences. Nucleic acid reassociation studies first revealed that humans and other primates contain multiple baboon endogenous virus (BaEV)-related sequences in their chromosomal DNA (6). A defective, endogenous provirus was recently isolated from a human recombinant DNA library by using as probe an endogenous chimpanzee retroviral pol fragment highly related to that of BaEV (7). This genome, termed HC-20 (or endogenous retrovirus-1; erv-1...