The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) removes mutagenic adducts from the O6 position of guanine, thereby protecting the genome against guanine : cytosine to adenine : thymine transition and, meanwhile, conferring tumor resistance to many anti-cancer alkylating agents commonly used in the treatment of malignant gliomas. Studies on the involvement of p53 protein in expression of the MGMT gene have provided conflicting results regarding the relation between p53 protein and MGMT gene expression. To examine the potential immunostaining pattern of MGMT expression and to evaluate the possible relationship between p53 and MGMT regulation, we assessed MGMT and p53 accumulation on 35 cases of diffusely infiltrating astrocytomas. With a few cases showing cytoplasmic staining, MGMT accumulation was mainly nuclear. The percentage of labeled tumor cells was lower in high-grade astrocytomas than in low-grade astrocytomas (P < 0.05). Additionally, p53-immunopositive tumor cells were usually immunonegative to MGMT. Thus, it is suggested that MGMT expression is reduced during malignant transformation of diffusely infiltrating astrocytomas, and that mutant p53 protein might be associated with down regulation of the MGMT expression.