Human monoclonal antibodies specific for the CD4-binding domain of HIV gp120 are useful in the neutralization of HIV and in the prevention of HIV infection and the treatment of a subject infected with HIV. Such antibodies and heterohybridomas producing them are disclosed. Synergistic mixtures of at least two human monoclonal antibodies specific for two different epitopes of gp120 are used to neutralize HIV, to prevent HIV infection and to treat a subject infected with HIV. In this synergistic mixture, one antibody has broad HIV group specificity, and is preferably specific for the CD4-binding domain. The other antibody is preferably specific for the V3 loop and has a range of neutralizing activity such that it neutralizes virus of the MN strain, MN-like families, and widely divergent HIV-1 isolates which are members of various V3 lop classes.