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