The effects of UV irradiation of skin on systemic immune responses are long-lasting (1-3 months). During this time, immune cells in peripheral tissues will be constantly replaced by cells from the bone marrow. We have previously published that CD11c+ cells (dendritic cells, DCs) cultured from bone marrow of mice after UV-irradiation of skin have reduced immunogenicity when transferred into naïve mice, and antigen-specific memory responses are attenuated. Prostaglandin E2 and an epigenetic process are involved directly or indirectly as the cyclooxygenase inhibitor, indomethacin, and an inhibitor of DNA methylation, 5-Aza-2-deoxycytidine, prevented the development from bone marrow of these less immunogenic DCs. To investigate DC development in vivo, bone marrow-ablated mice were engrafted with bone marrow cells from steady-state mice, UV-irradiated mice or mice implanted with pellets releasing 10 ug PGE2 per day. Sixteen weeks after bone marrow cell transfer, immune responses dependent on DC function were poor in recipients engrafted with cells from the bone marrow of UV/PGE2-administered mice. However, if wild-type bone marrow-derived DCs were injected into the UV/PGE2 chimeric mice, immune responses were restored to levels measured in control chimeric mice (i.e. engrafted with steady-state bone marrow cells). An effect of prostaglandin E2 on very early progenitors, possibly haemopoietic stem cells, is suggested. Further, when pregnant mice were UV-irradiated, DCs differentiating from the bone marrow of progeny were less immunogenic and further suggested an epigenetic effect of UVR. The attenuation of DC immunogenicity by PGE2 may be an important homeostasis.