Liposomes carrying molecules from trinitrophenylated epidermal cells (TNP-EC) liposomes stimulated the hapten-specific proliferation of lymphocytes in vitro in our previous study. In order to analyze the role of TNP-EC liposomes in vivo, they were injected into naive mice. TNP-EC liposomes induced contact sensitivity effectively when injected either s.c. or i.p. Contact sensitivity induced by TNP-EC liposomes was a long-lived T cell-mediated reaction. A s.c. injection of liposomes with molecules from TNP-Ia antigen-depleted epidermal cells [TNP-EC (Ia-) liposomes] failed to induce contact sensitivity and developed unresponsiveness. This unresponsiveness was transferred by T cells, i.e., suppressor T cells. Therefore, it is suggested that Ia antigens in epidermal cells play a critical role for induction and suppression of contact sensitivity.