Summary. Ovariectomized rats were given hormonal treatment mimicking progestational ovarian secretions. At maximal uterine sensitivity, the luminal epithelium was squeezed out of one or both horn(s) transected at the isthmus. Simultaneous bilateral scratching and saline injection induced virtually no response in stripped horns while contralateral intact horns exhibited a maximal decidual reaction (DCR). The luminal epithelium regenerated after ablation and a 65% DCR was again elicited after 9 days. The inability of de-epitheliated horns to decidualize was not overcome by intraluminal injections of the supernatant or sediment of the 60 000 g homogenate of epithelium, PGF-2α, PGE-2, arachidonic acid or histamine. Detachment of the epithelium without removal also prevented DCR induction. These results indicate that the luminal epithelium is an obligatory transmitter of the stimulus to DCR and cannot be by-passed by trauma. Release of the appropriate epithelial message to the stroma requires local preservation of membrane relationships between both tissues.