Sciatic endoneurial blood flow is reduced in experimental diabetes. This study examined the possible involvement of noradrenergic mechanisms in this impairment. In anaesthetised rats (pentobarbitone sodium 50 mg/kg, diazepam 2 mg/kg), sciatic nerve laser Doppler flux and vascular resistance in diabetic rats (5-6 weeks) were lower (approximately 50%) and higher (approximately 42%), respectively, than that in age-matched control rats, indicating nerve ischaemia in the diabetic tissues. Tyramine (1 nmol), noradrenaline (0.001-1 nmol) and phenylephrine (0.01-10 nmol) produced significant increases of nerve vascular resistance in control rats. The responses to tyramine (1 nmol) were completely blocked by desipramine (10 nmol) and those to phenylephrine (10 nmol) were reversed by phentolamine (1 nmol). In streptozotocin-diabetic rats, responses to phenylephrine or noradrenaline were enhanced compared to control rats, but the enhancement failed to reach statistical significance. The findings demonstrate that adrenergic stimulation affects sciatic nerve endoneurial blood flow.