The 5-methylcytosine content of c-myc proto-oncogene DNA obtained from samples of normal bladders and of bladders with transitional cell carcinoma of different stage and grade was analyzed. Five CCGG sites (from the third coding region to the 3' flanking region of the gene) which showed different methylation in normal and neoplastic samples were identified. The overall c-myc methylation levels were significantly reduced in carcinomas. Furthermore, a significant correlation between disease invasiveness and methylation level was found. Nevertheless, in each group of patients with the same histological grade, heterogeneity has been observed. This might be suggestive of different prognosis of the disease.