On the basis of previous studies that showed a negative association between HLA-A11 and skin cancer in renal transplant recipients and a positive association with HLA-B27 and HLA-DR7, we performed a study in Queensland with 1098 recipients to address the question of whether the same associations could be found. The influence of HLA mismatching and HLA homozygosity on the risk of skin cancer was also studied. In contrast to earlier studies, HLA-A11 was associated with an increased risk of skin cancer. On the other hand, we confirmed that the HLA-B27 antigen was associated with the development of skin cancer, but only when the development of basal cell carcinomas alone was considered, and we confirmed that there is a weak but not statistically significant association with HLA-DR7. No association between HLA mismatching or HLA homozygosity and the development of skin cancer was observed. Environmental factors such as different levels of exposure to sunlight and infection with human papillomaviruses are factors that are most likely to be involved. We hypothesize that human papillomavirus-induced antigens prevail in the skin cancers in the recipients living in the Netherlands, whereas antigens induced by solar radiation, the so-called "photo-antigens," may be more common in the skin cancers of the recipients living in Queensland. Exposure to sunlight can also induce immunologic unresponsiveness, and excessive exposure to sunlight in Australia may, therefore, simply override the risk factors that are important in countries with a more temperate climate.