The effects of several purinoceptor agonists and antagonists on norepinephrine overflow were examined in the electrically field stimulated vas deferens and saphenous artery of the rabbit. Both the adenine nucleotides ATP and beta,gamma-methylene ATP and the adenine nucleosides adenosine and 2-chloroadenosine reduced the electrical field stimulation-evoked release of norepinephrine from the in vitro vas deferens. These responses are antagonized by both 8-(p-sulfophenyl)-theophylline and alpha,beta-methylene ATP, indicating that this effect is mediated by P3-receptors. Interestingly, the nucleotide and nucleoside agonists facilitated, rather than inhibited, the electrical field stimulation-evoked release of norepinephrine from the in vitro perfused saphenous artery. This facilitation was antagonized by 8-(p-sulfophenyl)-theophylline but not by alpha,beta-methylene ATP. These results indicate that there may be facilitatory prejunctional purinoceptors that exhibit structure-activity relationships similar to, but perhaps not identical to, those exhibited by inhibitory prejunctional purinoceptors.