Young adult Sprague-Dawley rats of either sex were randomly assigned to be gonadectomized or left intact. Capsules containing either testosterone or estrogen were implanted in animals in both categories. Fifteen days after removal of the entorhinal cortex, the brains were analyzed for changes in reactive outgrowth of the commissural-associational afferent fibers in the hippocampal dentate gyrus. Both male and female control subjects showed identical sprouting responses. Only female subjects were significantly affected by gonadectomy, resulting in significant decreases in reactive fiber outgrowth. Hormone replacement therapy resulted in a return to control values in castrated females but had no affect on castrated males. The results suggest that sex hormones may regulate axon sprouting in the mature central nervous system.