1. The roles of autofeedback and neuronal uptake in neurotransmission produced by electrical field stimulation in several rabbit isolated blood vessels were examined. 2. Blocking drugs were used to separate the possible purinergic and noradrenergic contributions to the end organ response: prazosin, antagonist at postjunctional alpha 1-adrenoceptors; rauwolscine and yohimbine, antagonists at pre- and postjunctional alpha 2-adrenoceptors; alpha,beta-methylene ATP, desensitizing agent at postjunctional P2x-purinoceptors. In addition to desensitizing postjunctional P2x-purinoceptors, alpha,beta-methylene ATP potentiated the noradrenergic component of the nerve-induced responses. 3. In the presence of an intact neuronal uptake mechanism, the vessels showed different contributions of purinergic (via P2x-purinoceptors) and noradrenergic (via alpha 1-adrenoceptors and alpha 2-adrenoceptors) components to the end organ response to nerve stimulation: saphenous artery (approximately equal contributions from P2x-purinoceptors and alpha 1-adrenoceptors), ileocolic artery (mainly P2x-purinoceptors with a smaller contribution from alpha 1-adrenoceptors), plantaris vein (mainly alpha 1-adrenoceptors with a small contribution from alpha 2-adrenoceptors and P2x-purinoceptors) and saphenous vein (alpha 1-adrenoceptors). 4. The presence of alpha 2-adrenoceptor-mediated autofeedback could be demonstrated for both purinergic and noradrenergic components of the nerve-induced responses in the artery preparations. In the veins, potentiation of nerve-induced responses by alpha 2-adrenoceptor antagonists could not be studied due to blockade of postjunctional alpha 2-adrenoceptor-mediated vasoconstriction. 5. Blockade of neuronal uptake with cocaine potentiated the noradrenergic component of the nerve-induced responses. Both alpha 1-adrenoceptor- and alpha 2-adrenoceptor-mediated components were potentiated, with a relatively greater potentiation of the alpha 2-adrenoceptor-mediated component. In the case of saphenous vein an alpha 2-adrenoceptor-mediated component which was previously absent was uncovered.6. Blockade of neuronal uptake with cocaine had no effect or reduced the purinergic component of responses, the latter effect presumably due to enhanced alpha 2-adrenoceptor-mediated autofeedback.7. In the presence of cocaine, nerve-induced responses in the saphenous vein were biphasic. Rauwolscine potentiated the first phase and inhibited the second phase thus demonstrating effects of pre- and postjunctional alpha 2-adrenoceptor-mediated activation in the same preparation.8. In conclusion, neuronal uptake and autofeedback processes play important and complex interacting parts in determining the relative contributions of alpha 1,- and alpha 2-adrenoceptors and P2.-purinoceptors in the end organ response to neurotransmission in blood vessels.