OBJECTIVE Long standing ulcerative colitis (UC) has been known to be one of the precancerous diseases of colorectal cancer. Although the frequent loss of p53 allele (LOH) and aneuploidy were reported as the molecular events in carcinoma and dysplasia known as the precursor of UC, p53 genetic alteration was not reported in indefinite dysplasia and UC involved mucosa in long standing UC. Therefore, we investigated the mutational inactivation of the p53 gene in UC patients who showed dysplastic mucosa, as well as non-dysplastic mucosa on H & E stain and, secondly, if there is p53 mutation, we examined the relationship between p53 alteration and clinical data. METHODS Sixteen patients with UC who had different duration of colitis were studied by endoscopic examination with rectal mucosal biopsies, p53 gene alterations were detected by PCR-SSCP for exon 4-8 and immunohistochemical staining with p53 monoclonal antibody. RESULTS Among 16 patients, 2 patients (12%) showed dysplasia on H-E stain. The p53 point mutations were detected in 4 (two dysplasia and 2 normal looking mucosa) on PCR-SSCP. 4 patients who had p53 gene mutation were positive in immunohistochemical staining. With regard to clinical characteristics, these patients with p53 point mutation showed poor response to medical treatment. CONCLUSIONS These results suggest that the p53 mutation may be an early molecular event of cancerous change in UC.