Haptens, such as trinitrochlorobenzene (TNCB), bind to autologous skin proteins in the induction of allergic content sensitivity. In order to clarify the role of epidermal cells in the induction of allergic contact sensitivity in vivo, we used trinitrobenzene sulfonate (TNBS)-conjugated epidermal cells (TNP-EC) in attempts to sensitize syngeneic mice. Spleen cells conjugated with TNBS (TNP-SC) were used for comparison. Four to 28 days after injection (via various routes) of the haptenated cells, contact sensitivity was assessed by the application of the same hepaten to the ear. Sensitization regularly resulted from the subcutaneous infection of TNP-conjugated cells, and was longer lasting and was always stronger when TNP-EC were used rather than when TNP-SC were used. Neither TNP-EC nor TNP-SC injected intravenously resulted in allergic contact sensitivity, but both induced immunological hypo or unresponsiveness as assessed by subsequent painting with a sensitizing dose of TNCB. TNP-pvSC given intraperitoneally also did not sensitize and induced hyporesponsiveness which was in sharp contrast to the regular sensitization which resulted when TNP-EC were given intraperitoneally. Both similarities and differences in the abilities of haptenated epidermal cells and spleen cells to induce sensitization and tolerance are described and the results are discussed in relation to the role of antigen-presenting cells contained in the haptenated cell populations.