Major scientific obstacles blocking the development of a successful preventive HIV vaccine are the extraordinary variability of HIV, the lack of an exact animal model of HIV-induced AIDS, and the lack of understanding of the correlates of positive immunity to HIV. Current HIV vaccines containing the HIV gp120 envelope have been tested in phase I and II trials but they have had a major limitation of neutralizing only T-cell tropic laboratory-adapted HIV strains grown in T-cell lines, but not neutralizing HIV primary isolates. Phase III trials of monovalent HIV gp120 envelope vaccines are being planned in the US and Thailand, but concern has been raised that recombinant monovalent gp120 may not be an appropriate immunogen for an efficious HIV vaccine. Because the immune response is probably responsible for controlling the viral load in some long-term survivors of HIV infection, studies are now being carried out to induce similar immunity against a broad spectrum of strains of HIV primary isolates with targeted HIV experimental immunogens.