To investigate the transferability of macrophage (M Phi)-tropism among primate lentiviruses, we constructed recombinants of human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus strain mac (SIVmac) and chimeric HIV-1/SIVmac (SHIV) having env region M Phi-tropic determinants, A recombinant HIV-1 having env partially derived from a M Phi-tropic HIV-1 strain (JR-FL) replicated in human macrophages but not in monkey macrophages, Conversely, a recombinant SIVmac having env from a M Phi-tropic strain (SIVmac316) replicated in monkey macrophages but not in human macrophages, A new SHIV (designated NM-3rN/JRFL) carrying the LTR and gag, pol, vif, vpx and nef of SIVmac and vpr, tat, rev, vpu and env of HIV-1 with env partially replaced by that of JR-FL was replication-competent in human macrophages but not in monkey macrophages. These results suggest that the M Phi-tropic determinant is specific to each host species and that the mechanism of M Phi-tropism is different between HIV and SIV.