The network of interacting factors that control proliferation in the intestinal epithelium is largely unknown. Recently, IL-11 was found to protect animals from lethal doses of cytotoxic agents. Part of this protective action was ascribed to a reduced level of damage in the intestinal epithelium. Whether this was due to a direct effect on epithelial cell cycle progression was unclear. We have addressed this question in vitro and found that IL-11 reversibly inhibited proliferation in untransformed small intestinal IEC18 cells. However, IL-11 did not inhibit transformed SW620 or HT29 colonic cell lines. IL-6 behaved in a similar manner to IL-11. Thus, these results suggest that IL-11 may be an ideal therapy adjuvant, protecting normal cells and further, these results suggest that IL-11 may be involved in the normal growth controls in the intestinal epithelium. The inhibitory response evoked by IL-11 is lost during carcinogenic transformation.