Studies with experimental animals indicate that acetaldehyde, the first metabolite of ethanol that is microbially formed in the colonic lumen, may play a role in ethanol-associated colorectal co-carcinogenesis. Although intracoIonic acetaldehyde concentrations are highest during the metabolism of exogenous ethanol, some individuals may also possess marked amounts of endogenous acetaldehyde. Since no information is available concerning the possible effects of acetaldehyde on human colonic epithelial cells, this study was aimed to assess whether this compound, either alone or in combination with ethanol, affects such properties of human neoplastic colonocytes that are considered relevant with regard to cancer development. Human colon adenocarcinoma cell line Caco-2 was used as a model of transformed colonocytes, and effects of acetaldehyde and/or ethanol on the proliferation and differentiation of these cells as well as on their adhesion to collagens I and IV, the most important extracellular matrix proteins in the colon, were studied. The results of this study show that acetaldehyde markedly affects the phenotype of Caco-2 cells without having direct cytotoxic effects. Like many carcinogens, it was found to have a dual effect on cell proliferation rate, acute exposure being inhibitory and chronic exposure stimulating. Acetaldehyde also considerably decreased both sucrase activity and nuclear content of protein kinase A catalytic subunit in Caco-2 cells, which indicate that the differentiation of the cells was disturbed. Moreover, the adhesion of Caco-2 cells to collagens I and IV was dose-dependently reduced by acetaldehyde treatment. All these changes, i.e. enhanced cell proliferation rate (by chronic treatment), decreased differentiation, and reduced adhesion to extracellular matrix proteins, would in vivo predict more aggressive and invasive tumour behaviour. The possibility that colonic intraluminal acetaldehyde, either ethanol-derived or endogenous, might enhance the development of colorectal tumours should therefore be considered.