The modulation of noradrenaline (NA) release from rat spinal cord slices was investigated and the subtype of presynaptic alpha 2-adrenoceptors involved in the negative feedback modulation was characterized using in vitro perfusion experiments. Rat spinal cord slices were loaded with [3H]NA and the release of radioactivity at rest and in response to field stimulation was determined. The alpha 2-adrenoceptor agonists, clonidine and dexmedetomidine inhibited the stimulation-evoked release of NA from spinal cord slices, whereas alpha 2-adrenoceptor antagonists yohimbine and CH-38083 (7,8-(methylenedioxy)-14-alpha-hydroxyalloberbane HCI), enhanced it. ARC 239, a selective alpha 2B-antagonist, had no effect on the release. In contrast, BRL 44408 a selective alpha 2A-antagonist increased the release of NA. Our results indicate that the negative feedback modulation of NA release from noradrenergic fibres in the spinal cord is mediated via alpha 2A subtype of alpha 2-adrenoceptors.