DNA inoculation is capable of producing antigens intracellularly for ultimate presentation to the cellular and humoral components of the immune system and has potential for vaccine strategies against a number of infectious pathogens including HIV-1. It is well documented that the antigenic diversity of HIV-1 and its high level of nucleotide mutations during reverse transcription can lead to escape from immune surveillance. However, data suggest that a CD8-mediated cytotoxic T lymphocyte response may be less susceptible to escape mutants. We have shown previously that in vivo inoculation of rodents and non-human primates with plasmid expression vectors encoding HIV-1 gene products leads to production of HIV-1 antigens and results in the production of both cellular and humoral immune responses. In addition we have also demonstrated previously that these responses lead to protection in several in vivo models. We further demonstrate here that the cellular response induced is a type TH1 response and specific lysis of HIV-infected targets is CD8-mediated.