Since the P-2X purinoceptor has been shown to be homologous with RP-2, a gene activated in thymocytes undergoing apoptosis after glucocorticoid treatment, we have investigated the possible role of P-2X purinoceptors in thymocyte apoptosis. We report that P-2X purinoceptor mRNA is expressed both in untreated rat thymocytes and thymocytes treated with the synthetic glucocorticoid, 6 alpha-methylprednisolone, in a dose that can induce apoptosis. Furthermore, the P-2X receptor agonist, extracellular ATP, was unable to trigger apoptosis in rat thymocytes and had no effect on methylprednisolone-induced DNA fragmentation. Finally, the P-2X purinoceptor antagonists, suramin and pyridoxalphosphate-6-azophenyl-2',4'-dis acid, had no inhibitory effects on DNA fragmentation caused by methylprednisolone. Thus; our data demonstrate that P-2X purinoceptors are not directly involved in glucocorticoid-mediated thymocyte apoptosis.