The effect of ethanol on hippocampal axonal sprouting was studied with a histochemical technique for identifying acetylcholinesterase. Unilateral lesion of the entorhinal cortex in adult rats produced an increase in the density of acetylcholinesterase staining in the outer molecular layer and a concomitant increase in the width of the pale-staining commissural-associational zone of the dentate gyrus. Other rats were given ethanol (11.3 +/- 0.45 grams per kilogram) for 2 weeks before and 9 days after receiving the lesion. Ethanol abolished the expansion of the commissural-associated zone. The effect of ethanol on sprouting axons suggests that it may inhibit recovery of function after brain injury.