Irradiation with ultraviolet (UV) B light results in the formation of apoptotic keratinocytes called sunburn cells (SC). Although generation of SC appears to be one of the most characteristic features of UV-induced skin damage and has been a well-known phenomenon for a long time, the mechanisms involved are not quite clear. Recently, it was demonstrated that tumor necrosis factor alpha (TNF alpha) appears to be involved in the formation of SC since neutralization of TNF alpha both in vitro and in vivo reduced UVB-induced apoptosis of keratinocytes. Pentoxifylline is a methylxanthine derivative suppressing the release of TNF alpha. Therefore, we studied whether PTX is able to prevent the formation of SC. Addition of PTX to UVB-exposed HaCaT cells reduced DNA-fragmentation as examined by nick translation evaluated by flowcytometry. To prove whether PTX also reduces UVB-induced apoptosis in vivo, BALB/c mice were exposed to UVB on their abdomens, skin biopsies performed 24 h later and SC counted. A single dose of 2000 J/m2 caused a significant induction of SC which were remarkably reduced when PTX was injected intraperitoneally 3 h before and 12 h after UVB exposure. In summary, the data demonstrate that PTX can reduce the formation of SC both in vitro and in vivo and thus further support that TNF alpha is involved in UVB-induced apoptosis of keratinocytes.