Extracellular ATP regulates many hepatic functions by stimulating purinergic receptors. Only the G protein-coupled P2Y receptors have been studied in hepatocytes. We investigated the functional expression of P2X receptors, the ATP-gated channels in rat hepatocytes. P2X4 and P2X7 transcripts and proteins were detected by RT-PCR and by both Western blotting and immunocytochemistry. High concentrations of ATP, and 2'-and 3'-O-(4-benzoylbenzoyl)-ATP the preferring agonist of P2X7, induced membrane blebbing and significant uptake of 4-[(3-methyl-2(3H)-benzoxazolylidene)methyl]-1-[3-(triethylammonio)propyl]diiodide, both of which were inhibited by oxidised ATP, a blocker of P2X receptors. These results provide evidence that P2X4 and P2X7 receptors are expressed and functional on rat hepatocytes, possibly playing an important role in the purinergic signaling complex in these cells.