Relationship between nuclear accumulation of p53 protein and apoptosis induced by both DNA damaging agents (ultraviolet-irradiation and anticancer agents) and heat shock in normal human skin fibroblasts was investigated. Nuclear accumulation of p53 protein and apoptosis were induced dose-dependently by u.v. -irradiation and anticancer agents. Regarding heat shock treatment, intensive nuclear accumulation of p53 protein was induced by treatment at 43 degrees C for 45 min, but, apoptotic cells were never detected. These results indicated that accumulation of p53 protein and apoptosis induced by DNA damaging agents were considered to have a close relationship and the functions of induced p53 protein are different depending on the stimulating factor.