Physiologic overexpression of p53 protein may occur in the G1 stage of the cell cycle to slow down the cell cycle and allow DNA repair in stressed or injured cells. We questioned whether there is increased expression of p53 protein in acutely inflamed mucosa (AI) and regenerated mucosa (RM) in ulcerative colitis (UC) and Crohn's disease (CD). Formalin-fixed paraffin-embedded sections of resected bowels from eight patients with UC and 20 with CD were reviewed, and blocks were selected having areas defined as follows: AI = two high-power fields (HPFs) at the edge of an ulcer, or one HPF with an inflamed crypt in the center; RM = branched or irregular glands with only mild chronic inflammation. Blocks with normal mucosa were available in 20 cases. One case of CD also had dysplasia, adenoma, and invasive carcinoma. p53 was identified with PAb1801 antibody using a labeled avidin-biotin immunoperoxidase technique. In each defined area, the positive nuclei were counted and expressed as the number of positive nuclei per 10 HPFs. Data were analyzed statistically for comparisons within and between the diseases. In normal mucosa, only rare cells expressed p53 in two cases of CD. The mean frequency of positive nuclei was 2.24/10 HPFs in AI and 0.30/10 HPFs in RM in CD, and 7.63/10 HPFs in AI and 1.14/10 HPFs in RM in UC. Differences between the means for AI and RM were statistically significant in both UC and CD. Although not significant, the frequency of positive staining in both AI and RM was greater in UC as compared with CD.(ABSTRACT TRUNCATED AT 250 WORDS)