In the study the authors report that mice injected with supernatants from keratinocyte cultures exposed to UV radiation were impaired in host resistance to BCG. Both the induction and the elicitation of the delayed type hypersensitivity (DTH) reaction were suppressed following the intravenous injection of supernatants from the UV-irradiated keratinocytes, in a dose-dependent manner. Furthermore, injecting supernatants from the UV-irradiated keratinocytes interfered with the elimination of viable bacteria from the lymphoid organs. In order to determine whether macrophages were the target of the UV-induced keratinocyte-derived suppressive cytokine, macrophages were isolated from mice injected with the suppressive cytokine and the uptake and intracellular killing of BCG in vitro was studied. The suppressive cytokine and the uptake and intracellular killing of BCG in vitro was studied. The suppressive factor significantly reduced the uptake of BCG by the macrophages but not the rate of intracellular killing. These findings suggest that the suppressive cytokine interferes with the elimination of bacteria in vivo by interfering with the initial step in bacterial clearance, uptake of the bacteria by host macrophages. These results indicate that soluble mediators released from UV-irradiated keratinocytes may be involved in the UV-induced systemic suppression of immunity to BCG and they may act by interfering with certain macrophage functions.