T cells and macrophages invade dorsal root ganglia (DRGs) after sciatic nerve injury (1). We tested the hypothesis that this immune cell response is influenced by local sympathetic activity. L5 DRGs were evaluated one week after left sciatic nerve transection in rats in which, 10-14 days previously, L3 and L4 sympathetic ganglia had been removed either bilaterally or only ipsilaterally (sympathectomy), or the sympathetic chain had been cut just above L3 ganglion on both or only the ipsilateral side(s) (decentralization) (n=5 animals in each group). The procedures were performed in adult female Wistar rats anaesthetized with a mixture of ketamine 60 mg/kg and xylazine 10 mg/kg, i.p. for nerve lesions and with pentobarbitone 80 mg/kg i.p. for exsanguination and perfusion with fixative one week later. Sections of L5 DRGs and adjacent nerve trunks were investigated using fluorescence immunohistochemical techniques to identify lymphocytes positive for alpha/beta T-cell receptor (TCR) or CD8 and macrophages positive for major histocompatibility complex class II (MHC II), CD68 or CD163. The density of T-Iymphocytes and CD68+ and MHC II+ macrophages increased after sciatic nerve transection. When ipsilateral sympathectomy or ipsi- or bilateral decentralization preceded sciatic transection, mean alpha/beta TCR+ and CD8+ lymphocytes and MHC II+ and CD68+ macrophage densities in the lesioned DRGs were all ~35% lower than after sciatic transection alone, but the density of resident (CD163+) macrophages was similar in all groups of animals. Bilateral sympathectomy alone did not increase immune cell density in the DRGs but this intervention markedly enhanced the subsequent response to sciatic transection. Double labelling for CD8 and CD3 (a pan-T-cell marker) revealed that a few CD8+ cells were not CD3+ (i.e. they were macrophages). Analysis of the proportions of CD8-/CD3+ (i.e. CD4+) lymphocytes after each intervention revealed that the influx of CD4+ lymphocytes was markedly reduced after removal of sympathetic activity. It is concluded that local sympathetic activity influences immune cell invasion into dorsal root ganglia after peripheral nerve injury.