The presence of the Na /Ca² exchange mechanism was investigated in porcine oocytes. Immature and in vitro-matured oocytes were loaded with the Ca² -sensitive fluorescent dye fura 2 and changes in the intracellular free Ca² concentration ([Ca² ]_i) were monitored after altering the Na concentration gradient across the plasma membrane. Decreasing the extracellular Na concentration induced an increase in [Ca² ]_i possibly by a Ca² influx via the Na /Ca² exchanger. A similar Ca² influx could also be triggered after increasing the intracellular Na concentration by incubation in the presence of ouabain (0.4 mM), a Na /K -ATPase inhibitor. The increase in the [Ca² ]_i was due to Ca² influx since it was abolished in the absence of extracellular Ca² , and the increase was mediated by the Na /Ca² exchanger since it was blocked by the application of amiloride or bepridil, inhibitors of Na /Ca² exchange. Verapamil (50 μM) and pimozide (50 μM), inhibitors of L- and T-type voltage-gated Ca² channels, respectively, could not block the Ca² influx. The Ca² entry via the Na /Ca² exchanger could not induce the release of cortical granules and did not stimulate the resumption of meiosis. This was unexpected because Ca² is thought to be a universal trigger for activation. Using antibodies raised against the exchanger, it was demonstrated that the Na /Ca² exchanger was localized predominantly in the plasma membrane. Reverse transcription-polymerase chain reaction revealed that porcine oocytes contain a transcript that shows 98.1% homology to the NACA3 isoform of the porcine Na /Ca² exchanger.