Following cholinergic denervation of the hippocampal formation, via medial septal lesions, sympathetic fibers, originating from the superior cervical ganglia, grow into the hippocampus. Previous studies have demonstrated a detrimental effect of these fibers on recovery of a spatial-learning task in male but not female animals. In this study we assessed the role of circulating male sex hormones on the behavioral and biochemical effects of hippocampal sympathetic ingrowth (HSI). For the behavioral studies male Sprague-Dawley rats underwent either sham gonadectomy or gonadectomy and were taught a standard radial 8-arm maze task. Following attainment of criterion animals underwent one of three surgical procedures: sham surgery, MS lesions, MS lesions + ganglionectomy. MS lesions, regardless of the presence of HSI, were found to severely impair reacquisition of the task in both sham-gonadectomized and gonadectomized animals. As expected, in the sham-gonadectomized group, MSGx animals reacquired the task faster than the MS group. However, gonadectomy was found to block the detrimental effect of HSI on behavior. For the biochemical studies hippocampal norepinephrine (NE) and choline acetyltransferase (ChAT) were measured eight weeks after surgery in sham-gonadectomized and gonadectomized animals. MS lesions were found to significantly reduce the ChAT activity, regardless of circulating sex hormones. Gonadectomy was found to significantly reduce the level of NE associated with HSI, while having no effect on central NE in CON or MSGx animals. These studies suggest that circulating male sex hormones can influence both the behavioral and biochemical processes associated with HSI. © 1990.