The capacity of interferon-γ (IFN-γ) to induce class II histocompatibility antigens on different cell types including keratinocytes, is well known, but the impact of IFN-γ on the immune response is still unclear. Lewis rats sensitized with dinitrofluorobenzene (DNFB) were injected with recombinant rat IFN-γ (10⁵ U) or phosphate-buffered saline (PBS) once daily on 3 successive days at the bases of the ears either before or after they were challenged on the ears. As expected, the PBS-treated animals showed about a 30% increase in ear thickness and there was an induced expression of class II antigens on the keratinocytes as judged by immunohistochemistry 72 h after challenge. Exogenously added IFN-γ prior to DNFB challenge resulted in a significantly reduced ear swelling at 24 (p<0.01) and 48 h (p<0.05) after challenge. In this case the keratinocytes expressed class II antigens already at the time of challenge. When IFN-γ injections were given during the contact allergic reaction there was no significant reduction of ear swelling until 72 h (p<0.01). At that time point there was a more pronounced expression of class II antigens on the keratinocytes compared with PBS-injected animals, due to the IFN-γ treatment. These in vivo data support our previous observations that IFN-γ may play a self-limiting role in certain immune responses.