Effects of extracellular Na+ on platelet responses were examined. Cytoplasmic pH decreased by stimulation with thrombin, TPA and AA in Na(+)-containing buffer as well as in Na(+)-free buffer. Thrombin-induced aggregation and serotonin release were higher in Na(+)-containing buffer, but TPA- and A23187-induced responses exhibited lower values. Thrombin-stimulated platelet in Na(+)-free buffer started to aggregate by the addition of NaCl. Inhibition of thrombin-induced aggregation by indomethacin was apparently weaker than that by removal of Na+. These results suggest that the changes of platelet responses by removal of Na+ is due to the effect of Na+ ion itself, not by the inhibition of Na+/H+ exchanger, and that Na+ affects on mechanisms other than arachidonic acid mobilization.