Enhancement of virus infectivity after sCD4 treatment has been documented for SIVagm and HIV-2. It has been suggested that a similar phenomenon may play a role in HIV-1 infection. In the present study we have analysed biological activities of virus neutralizing polyclonal and monoclonal human antibodies and of sCD4, towards HIV-1 chimeras with envelope proteins derived from one donor, which display different biological phenotypes. The antibodies, which recognize the V3 and/or the CD4 binding domains of the glycoproteins of these viruses and also sCD4 showed different levels of virus neutralizing activity toward the syncytium inducing HIV-1 strains. In contrast, they all dramatically enhanced the infectivity of an HIV-1 chimera with an envelope glycoprotein displaying the non-syncytium-inducing phenotype. Given the relatively conserved nature of non-syncytium-inducing HIV-1 surface glycoproteins early after infection, these data suggest a major role for antibody mediated enhancement of virus infectivity in the early pathogenesis of HIV-1 infection.