Because interleukin (IL)-10 is an immunoregulatory cytokine that is produced by keratinocytes exposed to UVB radiation (UVR), we determined whether IL-10 participates in either failed contact hypersensitivity (CH) induction or tolerance after acute, low-dose UVR. Murine recombinant IL-10 (200 ng) was injected intradermally on shaved abdominal skin. To assess the effects of IL-10 on CH induction, dinitrofluorobenzene (DNFB, 185 μg) was painted on the skin within 30 min after IL-10 was injected, and the mice were assayed 5 d later by ear challenge with dilute DNFB. To assess tolerance, DNFB (185 μg) was painted a second time on normal body-wall skin 14 d after DNFB was first painted on IL-10-injected skin; CH was then assayed on day 19. We found that mice that received DNFB on IL-10-injected skin developed CH comparable in intensity to that observed in PBS-injected controls. Thus, this dose of IL-10 did not prove to be deleterious to CH induction if hapten was painted on the injected site within 30 min. By contrast, mice that first experienced DNFB within 30 min, 1 d, or 3 d after IL-10 had been injected intracutaneously displayed hapten-specific tolerance. Moreover, intraperitoneally injected anti-IL-10 antibody prevented UVR- and cis-urocanic acid-dependent tolerance; anti-IL-10 antibody had no effect on TNF-α-induced tolerance and failed to restore CH induction after UVR exposures. These data indicate that IL-10 is an important mediator of the tolerance induced when hapten is painted on the skin of animals exposed to acute, low-dose UVR.