One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-1). In this study we found that pseudotypes allow penetration of HIV particles into CD-I-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could he blocked with anti-HTLV-l serum hut failed to be significantly inhibited with anti-HlV serum or a V,-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility for pseudotypes to escape neutralization by the immune system in vivo. Pre vious reports have suggested that carbohydrate structures may be conserved neutralization epitopes on retroviruses. In this study, the neutralizing capacity of lectins and anti-carbohydrate monoclonal antibodies was found to block infection by cell-free pseudotypes in CD-I-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo. HIV and HTLV-1 seem to induce common carbohydrate neutralization epitopes.