Recently a 17p deletion and p53 gene mutations were reported in human gliomas, but the relationship of the timing of p53 gene mutation and oncogenesis of glioma is still obscure. We examined eight pairs of primary and recurrent gliomas. Four of eight had a histological malignant transformation. In the group with malignant transformation, three out of four pairs had a mutation in the p53 gene only in recurrence. None of the mutations in either primary or recurrent glioma was detected in the group with no histological change. All point mutations occurred within the evolutionarily conserved regions. This suggests that the p53 mutations occurred during the progression and were important in the malignant transformation in the some kinds of gliomas.