Ultraviolet radiation (UVR) of the UVB- and UVA-region suppresses immunity and in the dose relation manner it induces cutaneous or systemic state of immunotolerance. It was proved by the successful experimental transplantation of a tumor graft to the skin of UV-radiated animals and on the other side by unsuccessful attempts at skin contact-sensitization. UVR induces this condition either by direct inhibition of antigen-presentating function of the Langerhans cells, or indirectly by the stimulation of secretion of immunomodulatory cytokines in keratinocytes. UVR inhibits also functions of the natural killer cells in apoptotic and lytic cell-processes. It directly correlates with carcinogeneity in conditions of the dysbalance in developing expression of the tumor-suppressive gene p53, mutated by the irradiation and that of bcl-2 gene preventing apoptotic changes in somatic cells. Moreover, the immunosuppression is enhanced by the isomerization of urocanic acid and by the development of damaged DNA-photoproducts. Also various neuropeptides, namely propiomelanocortin, have their partial role in immunomodulation. Local photoprotective substances prevent UVR-penetration into the skin and thus block the immunosuppressive effects in relation to their chemical composition and to the SPF (solar photoprotective factor) value. Their effect depends on the width of the UVR-region blocked, which should include both the UVB and UVA band, and also on the concentration, chemical stability and on the method of their application.