Exposure to ultraviolet (UV) radiation can modulate immune responses in animal and humans. Remarkably, the UV-induced immunosuppression is not restricted to the exposed skin but is also found at other body sites, i.e. systemic Immunosuppression. Effects of UV radiation on infections cannot be determined by experimentation on humans, but the effects of UV on vaccination may serve as a model. Moreover, it is important in its own right whether UV radiation affects vaccination responses. In the present study, the effect of UVB exposure on the development of immune responses after hepatitis B vaccination in human volunteers (n=191)was investigated. Volunteers were exposed to UVB on 5 consecutive days (1 MED/day) followed by a standard hepatitis B vaccination protocol. Although the UVB exposure regime was sufficient to suppress cutaneous hypersensitivity responses and NK activity, antigen-specific humoral (anti-HBs) and cellular immunity (proliferation induced by HB-sAg) were not significantly affected. For all volunteers single nucleotide polymorphisms (SNPs) have been determined for the following interleukines: IL-1RA (+2018), IL-l alaph (+4845), IL-1 beta (+3953), TNF-alpha (-308) and TNF-alpha (-238). These polymorphisms, and most importantly for IL-lRA, lL-1alpha and IL-beta, affect quantitatively the production of the corresponding interleukines. and may thereby play a role in the susceptibility to UVB-induced immunomodulation. Taking into account these polymorphisms, it was demonstrated that humoral and cellular immune responses to the hepatitis B vaccine as well as the susceptibility to UVB-induced immunomodulation depends on the type of polymorphism. We conclude therefore that UVB exposure prior to hepatitis B vaccination does not affect either humoral nor cellular responses at a population base. However, when study objects are subdivided according to their interleukin polymorphism profile, differences in vaccination responses as well as in UVB-induced immunomodulation of these responses can be observed.