The present investigation was undertaken to study the inactivation of endogenous noradrenaline (NA) released by electrical stimulation of the dog saphenous vein strips. Electrical stimulation of this preparation caused contractile responses which were due to release of NA. Relaxation curves were determined after oil immersion. Cocaine (10–5 m) blocked the greatest part of the inactivation capacity showing that most of the released NA that acts on the α-adrenergic receptors is taken up by sympathetic nerves. Neither monoamine oxidase (MAO) nor catechol-O-methyl transferase (COMT) nor uptake2 seem to play important roles in the inactivation of endogenous NA. After blockade of neuronal uptake by cocaine, both cortexone (6 × 10–5 m), an inhibitor of uptake2, and U-0521 (10–4 m) (3,4-dihydroxy-2-methyl propiophenone), an inhibitor of COMT, blocked a significant part of the remaining inactivation capacity showing that uptake2 and COMT metabolism can represent an alternative to neuronal uptake. After cocaine, iproniazid (7 × 10–4 m) was ineffective. The relative roles of the different mechanisms of inactivation of endogenous NA are different from those for exogenous NA in the dog saphenous v