PURPOSE: We investigate whether p16 INK4 and p15 INK4B inhibit cellular proliferation and exert a growth suppressive effect on esophageal cancer cells. MATERIALS AND METHODS: The growth suppressive effects of p6 INK4 and p15 INK4B were evaluated by transfecting vectors containing the p16 INK4 cDNA or the p15 INK4B cDNA, or both, constitutively driven by a cytomegalovirus promoter, into two human esophageal cancer cell lines containing or lacking endogenous p16 INK4 and/or p15 INK4B. RESULTS: These experiments demonstrated that in both cells lines tested, the numbers of cells surviving dramatically decreased in p16 INK4-transfected and p15 INK4B-transfected cells compared with control vector-transfected cells. There was no significant difference in the degree of growth inhibition between p16 INK4-transfected and p15 INK4B-transfected cell lines. CONCLUSIONS: These results suggest that p16 INK4 and p15 INK4B play important roles in the initiation or promotion of esophageal cancer. The inactivation of p16 INK4 and p15 INK4B may contribute to uncontrolled growth in human cancer.