Cells in the human intestinal epithelium have a life-span of around 5 days before being lost by apoptosis at the luminal surface. We examined changes in expression of the Bcl-2 gene family which may be responsible for epithelial cell loss. In the normal and neoplastic colon, mucosal expression of immunoreactive Bak co-localized with sites of epithelial cell apoptosis. Inducing apoptosis in the human colon cancer cell line HT29 and the rat normal small intestinal cell line IEC 18 in culture was accompanied by increased Bak expression without consistent changes in expression of other Bcl-2 homologous proteins. Bak appears to be the endogenous Bcl-2 family member best correlated with intestinal cell apoptosis.