We have determined the nucleotide sequence in the U3-R regions of the long terminal repeat (LTR) associated with NFS-Th-I xenotropic murine leukemia virus (MuLV) DNA The RNA genome of type C retroviruses contains terminally redundant sequences (R) that are located adjacent to segments unique to the 5' (U5) and 3' (U3) termini (1). After infection, the viral RNA is reverse transcribed into double-stranded DNA, which subsequently becomes integrated into cellular chromosomal DNA (2, 3). Both the unintegrated and integrated copies of proviral DNA contain terminally duplicated sequences derived from each end of the viral genome forming a structure (U3-R-U5) referred to as the long terminal repeat (LTR). LTRs contain important regulatory signals for the promotion, initiation, and processing of viral mRNAs and may play a role in the integration of proviral DNA into the host chromosome (3). Furthermore, nucleotide sequence analyses show that LTRs possess structural features characteristic of transposable elements found in bacteria, yeast, and Drosophila (4)(5)(6)(7)(8)(9)(10)(11).In several vertebrate species, DNA copies of type C retroviruses have been identified as genetically stable integral components of chromosomal DNA (12). Such endogenous proviruses have been shown to be vertically transmitted, can be mapped to specific chromosomal loci, and, in some cases, may be expressed as infectious retroviruses (12). We Because we had previously shown that the LTRs associated with endogenous MuLV proviruses could be distinguished from the LTR segments associated with known infectious viruses (13) and since the numerous copies of these elements present in mammalian chromosomal DNA could potentially regulate the expression of adjacent cellular genes, we determined the nucleotide sequences in the U3 R regions of five endogenous LTRs. The results of these sequence analyses and comparisons with LTRs associated with infectious xenotropic, ecotropic, and MCF proviruses are presented.MATERIALS AND METHODS Recombinant DNA Clones. The Pst I/Sma I segment derived from the U3-R region of the LTRs associated with the endogenous BALB/c MuLV proviral DNA clones B-56, B-73, B-14 (5' LTRs), and B-34 (3' LTR) (13) and with NFS-Th-1 xenotropic DNA cloned from MuLV-infected cells (14) The publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.