Following cholinergic denervation of the hippocampal formation, via medial septal (MS) lesions, sympathetic fibers, originating from the superior cervical ganglia, grow into the hippocampus. Previous studies have demonstrated a sexually dimorphic effect of this neuronal rearrangement on recovery of a spatial-learning task, with this rearrangement being detrimental in male but protective in female rats. Circulating male sex hormones were found to interact with this effect in male animals. In this study we assessed the role of circulating female sex hormones on the behavioral and biochemical effects of hippocampal sympathetic ingrowth (HSI). For the behavioral studies female rats underwent either sham ovariectomy (sham OVARX) or OVARX 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 + sham ganglionectomy (MS); HSI group; MS lesions + ganglionectomy (MSGx). As in our previous study, animals with HSI (i.e. MS group) were found to recover learning faster (in fact, these animals did not differ from controls) than animals with MS lesions without HSI. Gonadal status did not affect this behavioral recovery. For the biochemical studies hippocampal norepinephrine (NE) and choline acetyltransferase (ChAT) were measured in animals sham OVARX and OVARX, 8-12 weeks after the neurosurgical procedure. MS lesions (i.e. MSGx; MS) were found to reduce ChAT activity, regardless of circulating sex hormones. In controls NE levels were similar between OVARX and sham OVARX. NE levels were markedly elevated in the OVARX MS group compared to all other groups including sham OVARX. In the MSGx groups, NE levels were reduced compared to controls, while comparisons between these groups revealed a significant reduction in NE levels in the OVARX MSGx group compared to sham OVARX MSGx group. These studies suggest that female circulating sex hormones interact with brain injury in a very complex manner. However, this interaction does not appear to mediate the changes in behavior observed after HSI. © 1993.