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 (TD,-TD 1 ?was able to induce cytotoxic T lymphocytes in vivo. Interestingly, this induction cou d 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 TD, contained within the sequence of the TD, RIQRGPGRAPVTIGK from the immunodommant V3 loop of HIV1 gp120. The possible implications of these findings in HIV infection and AIDS disease are discussed.