Suramin, currently reported as a P2 purinoceptor antagonist, competitively inhibited P2 purinoceptor agonist-induced phospholipase C (PLC) stimulation, but not P2 purinoceptor agonist-induced adenylate cyclase (AC) inhibition in rat hepatocytes. Suramin did not inhibit vasopressin-induced PLC activity. We conclude that there are two types of P2 purinoceptors; one is suramin-sensitive and coupled to PLC in a stimulatory manner, and the other is suramin-insensitive and coupled to AC in an inhibitory manner.