The macaque/SIV animal system is an important model for studying AIDS pathogenesis and for evaluating the efficacy of vaccines and anti-viral therapeutics. However, differences between HIV-1 and SIV envelope proteins exist that render the SIV/macaque model of limited value when examining envelope determinants of retroviral pathogenesis. To overcome this problem, we utilized a chimeric virus, SHIVSF33, containing the env gene from HIV-1SF33 in the context of the molecular clone SIVmac239, in the macaque animal model. In this study SHIVSF33A, a pathogenic virus that evolved in vivo from a rhesus macaque infected intravenously with the molecular clone SHIVSF33 was used in both in vitro and in vivo studies. By using a cell culture system, we examined the biological properties of our parental and animal-adapted chimeric viruses and compared in vitro susceptibility to in vivo studies.