In rat parotid acinar cells, ATP caused a transient increase in the intracellular Ca2+ concentration ([Ca2+]i) in the absence of external Ca2+. The ATP-induced Ca2+ response was strongly suppressed by removal of external Na+. The sequence of potency in increasing [Ca2+]i was 3'-o-(4-benzoyl) benzoyl-ATP > ATP > uridine 5'-triphosphate (UTP). Adenosine, AMP, ADP or alpha,beta-metylene ATP did not cause an increase in [Ca2+]i. The 3'-o-(4-benzoyl) benzoyl-ATP-induced increase in [Ca2+]i was abolished by removal of external Na+, but the UTP-induced response was not. The threshold external Na+ concentration required for ATP- or 3'-o-(4-benzoyl) benzoyl-ATP-induced Ca2+ release was 10-20 mM. ATP but not UTP caused a rise in the intracellular Na+ concentration ([Na+]i). Ca2+ release stimulated by caffeine or treatment with ryanodine reduced the Ca2+ release evoked by ATP. These results suggest that ATP, acting through P2Z purinoceptors, causes Na+ entry by opening cation-permeable channels, and thereafter the increase in [Na+]i triggers Ca2+ release from ryanodine-sensitive stores. UTP, acting through P2U purinoceptors, causes Ca2+ release independent of external Na+.