Immunization of mice with peptide constructs, consisting of a determinant recognized by T cytotoxic cells colinearly linked to a determinant recognized by T helper cells (TDc-TDh) was able to induce cytotoxic T lymphocytes in vivo. Interestingly, this induction could be achieved in the absence of adjuvant in non-depleted as well as in CD4(+)-cell-depleted BALB/c mice. In the latter case, induction took place simultaneously with the activation of CD8+ T helper cells specific for a TDh contained within the sequence of the TDc RIQRGPGRAFVTIGK from the immunodominant V3 loop of HIV1 gp120. The possible implications of these findings in HIV infection and AIDS disease are discussed.