This report deals with the molecular characterization of a representational difference analysis (RDA)-derived sequence (SZRV-2, GenBank accession No. AF135486; Genome Database accession Nos. 7692183 and 7501402) from three monozygotic twin pairs discordant for schizophrenia (MZD). The results suggest that it is a primate-specific, heavily methylated, and placentally expressed (-7-kb mRNA) endogenous retroviral-related (ERV) sequence of the human genome. We have mapped this sequence to 12q13 using two SZRV-2 positive BAC clones (4K11 (Genome Survey Sequence Database No. 1752076; GenBank accession No. AZ301773) and 501H16) by fluorescence in situ hybridization. End sequencing of the 4K11 BAC clone has allowed identification of nearby genes from the human genome database at NCBI that may be of interest in schizophrenia research. These include viral-related sequences (potential hot spots for insertions), developmental, channel, and signal transduction genes, as well as genes affecting expression of certain receptors in neurons. Furthermore, when used as a probe on Southern blots, SZRV-2 detected no difference between schizophrenia patients from southwestern Ontario and their matched controls. However, it identified aberrant methylation in one of the eight patients and none of the 21 unaffected controls. Although additional experiments will be required to establish the significance, if any, of SZRV-2 methylation in the complex etiology of schizophrenia, molecular results included offer a novel insight into the role of retroviral-related sequences in the origin, organization, and regulation of the human genome.