Contact hypersensitivity (CHS) to picryl chloride (PCl) is depressed in C57BL/6 mice when CHS is induced via early anagen skin. We have now further dissected this phenomenon in vivo. The elicitation phase for CHS was suppressed when anagen was induced 4 days after PCl sensitization of telogen animals. Sensitization of mice via abdominal skin with all hair follicles in telogen, and back skin follicles in anagen, significantly reduced the magnitude of the ear swelling response. Consecutive applications of two sensitizing doses of hapten, first on induced anagen back skin and then on telogen abdominal skin 7 days later, failed to induce tolerance. Furthermore, spleen cell transfer of sensitized anagen mice into telogen mice did not inhibit CHS response in the recipients. The current study suggests that a temporary state of systemic hyporesponsiveness, mediated, e.g., by hair cycle-dependent production of immunosuppressive cytokines rather than hapten-specific T suppressor cell activities, plays a critical role.