We examined the effect of ethanol on lesion-induced sprouting in the molecular layer of the dentate gyrus. Adult rats were fed a liquid diet containing either ethanol or sucrose for 14 days before and 9 days following unilateral entorhinal cortex lesions. One group was provided the ethanol diet ad libitum during both the pre- and postlesion period. Three other groups were pair-fed to the latter group; one consumed ethanol prelesion, one postlesion, and one did not receive ethanol. Sections through the rostral hippocampus were stained for histochemical localization of acetylcholinesterase. Following the entorhinal lesion the pale-staining commissural/associational zone ipsilateral to the lesion typically expands and exhibits decreased acetylcholinesterase staining. When ethanol was administered after the lesion, expansion of the commissural/associational zone was significantly diminished compared with the two groups that received the control diet after the lesion. Ethanol administered for 2 weeks before the lesion had no measurable effect on commissural/associational zone expansion. These findings imply that, at least for short-term exposure, ethanol reduces the sprouting responsiveness of systems in the dentate gyrus only during the postlesion period when sprouting normally occurs.