Apoptosis represents an active cell death which contributes not only to the regulation of tissue homeostasis but in addition to the deletion of DNA-damaged single cells. We could recently show that UV-A and UV-B irradiation results in a dose- and time-dependent induction of apoptosis in HaCaT keratinocytes. The present study was aimed at elucidating whether the tumor suppressor gene p53 plays a role in UV-induced apoptosis of these cells. Apoptosis was determined by means of light and electron microscopy and by a specific ELISA for determination of DNA-fragmentation. Western blot analysis and immune electron microscopy studies revealed a nuclear accumulation of p53 which ran in parallel to the induction of apoptosis by UV-B irradiation. Addition of vitamin D 3 , EGTA, acetylcysteine prior to UV irradiation resulted in both reduced expression of p53 on the protein level and reduced apoptosis. In contrast, the protein synthesis inhibitor cycloheximide slightly enhanced p53 expression and apoptotic changes after UV-B irradiation. Our data suggest that p53 is involved in the induction of apoptosis in HaCaT keratinocytes and is modulated by substances known to affect apoptosis in other cell types.