A xenotropic murine leukemia virus-related virus (XMRV) has been reported to be an emerging pathogen associated with prostate cancer (PC) and chronic fatigue syndrome (CFS). However, recent studies have demonstrated that XMRV is a laboratory-derived virus resulting from genetic recombination between two mouse viral genomes during serial xenograft tissue transplantation. This study describes a phylogenetic analysis that compared XMRV with the ecotropic murine leukemia viruses (E-MLV), xenotropic MLV (X-MLV), and other retroviruses, including HTLV-1 and HIV-1. We found that sequences corresponding to three XMRV structural proteins (Env, Gag, and Pol) exhibited high degrees of homology with X-MLV (>91 %) and E-MLV (67-96 %), but not HTLV-1 (13-16 %) or HIV-1 (10-15 %), indicating that XMRV was derived from X-MLV and/or E-MLV. We then compared the infectivity of XMRV and E-MLV for human and murine lymphocytes, respectively. Results showed that human PBMCs were not susceptible to XMRV infection, suggesting that XMRV exhibits host cell tropism similar to E-MLV that only infects murine PBMCs. These data suggest that it is unlikely that this laboratory-generated retrovirus could cause disease in humans.