Current evidence suggests that the induction of cell-mediated immunity is required for a successful HIV-1 vaccine. Delayed type hypersensitivity (DTH) and cellular cytotoxicity are closely linked elements of the cellular immune response, both are favored by immunizations that result in a T-helper (Th)-1 response. The classical experimental animal for the study of DTH is the guinea pig. Here we report that guinea pigs can readily be sensitized for DTH skin reactions to envelope protein with a plasmid expressing HIV-1(MN) (subtype B) envelope, as well as with the recombinant HIV-1 envelope protein. Further, utilizing peptide probes that in aggregate represent the entire gp120 molecule, common and unique dominant epitopes induced by each method of immunization were identified.