1 The effect of pyridoxal 5-phosphate, and the 2',4' and 2',5'-disulphonic acid isomers of 6-azophenyl-pyridoxal 5-phosphate (PPADS and IsoPPADS respectively) on depolarization of the rat superior cervical ganglion evoked by alpha,beta-methylene-adenosine 5'-triphosphate (alpha,beta-Me-ATP) and uridine 5'triphosphate (UTP) were determined by a grease-gap recording technique. 2 Pyridoxal 5-phosphate (10-100 mu M) and PPADS (10-100 mu M) enhanced UTP- and depressed alpha,beta-Me-ATP-evoked depolarizations but did not significantly alter depolarizations evoked by potassium or hyperpolarizations evoked by adenosine. IsoPPADS (10 mu M) depressed alpha,beta-Me-ATP-evoked depolarizations but did not alter depolarizations evoked by UTP. Depolarizations evoked by muscarine were depressed by IsoPPADS but not by pyridoxal 5-phosphate. 3 It is concluded that pyridoxal 5-phosphate, PPADS and IsoPPADS are antagonists at P-2X-purinoceptors but not at the receptors that mediate UTP-evoked depolarization of the rat superior cervical ganglion. These observations substantiate the recent proposal that the rat superior cervical ganglia possess distinct receptors for purine and pyrimidine 5'-nucleotides, i.e. P-2X-purinoceptors and pyrimidinoceptors respectively.