Expression of bcl-2 oncoprotein (Bcl-2) in carcinomas and their precursor lesions in the colon, stomach, uterine cervix (squamous and glandular epithelium), and endometrium was examined immunohistochemically using clone 124 monoclonal antibody. Most cases of premalignant lesions in the colon (adenoma, 80.6%), stomach (metaplastic gastritis, 77.1%, mainly positive in the proliferative zone), endocervix (glandular dysplasia, 87.5%) and endometrium (endometrial hyperplasia, 65.4%) showed intense immunoreactivity for Bcl-2, whereas fewer than 30% of adenocarcinomas in these tissues had no or weak Bcl-2 expression. In the stomach, adenomas with definite Bcl-2 expression were 37.5% of the cases examined. Conversely, most of both squamous intraepithelial neoplasia and squamous cell carcinoma of the uterine cervix showed weak or no Bcl-2 expression. These results suggest that upregulation of Bcl-2 in premalignant lesions and downregulation after malignant change is, to some extent, a common event in the glandular system, but not in the squamous epithelium of the uterine cervix. Bcl-2 may play an important role in keeping the transformed cells alive at the early stage of multistep carcinogenesis in the glandular tissue by an escape from a regulatory mechanism of apoptosis for further accumulation of gene abnormalities.