HLA-specific antibodies generated by allo-immunization are supposed to be involved in the control of HIV infections by both the neutralizing capacity of HLA-specific antibodies (Abs) and HLA-specific Ab-dependent complement-mediated lysis (CML). We further characterized CML of HIV primary isolates induced by HLA-specific Abs. Although HIV-specific and HLA allo-type specific Abs induced only weak CML of HIV primary isolates, several combinations of HLA allo-type specific Abs with HIV-specific Abs could enhance CML significantly. Nevertheless, certain HLA-specific Abs did not improve but even inhibit CML of HIV, although the corresponding HLA molecules were present. Thus, our results emphasize a possible limitation of allo-immunization as a potential approach to induce protective immunity against HIV.