We examined the role of the p53 gene in hyperthermia-induced apoptosis using three human gastric carcinoma cell lines, MKN-28 (carrying mutated type p53 gene), MKN-74 (wild-type), and KATO-III (complete deletion). The results indicate that i) long-term hyperthermia causes necrosis, and short-term treatment induces apoptosis in a gradual time dependent fashion, ii) hyperthermia-triggered apoptosis can occur both in a p53 gene-dependent and -independent manner, and iii) up-regulation of Hsp70 might enhance the function of wild-type p53 protein in hyperthermia-induced apoptosis.