Using the fluorescent dyes sodium-binding-benzofuran-isophthalate and fura-2 cytosolic free sodium concentration ([Na+]i) and cytosolic free calcium concentration ([Ca2+]i) were investigated in intact human platelets in order to characterize the effect of elevated [Ca2+]i on [Na+]i. Spectrofluorometric studies of [Ca2+]i and [Na+]i in intact platelets were done after specific inhibition of endoplasmic Ca-ATPase by thapsigargin. Thapsigargin increased [Ca2+]i and [Na+]i in platelets. Addition of thapsigargin increased [Na+]i from 23.5 +/- 2.9 mM to 51.6 +/- 11.1 mM (mean +/- S.E., P < 0.05). The thapsigargin induced [Na+]i increase was also seen in the absence of extracellular calcium. In the absence of external sodium the thapsigargin induced [Na+]i increase was abolished, indicating that thapsigargin induced [Na+]i increase was due to sodium influx. Thapsigargin induced sodium influx was blocked after administration of NiCl2. The present results support the idea that the filling state of intracellular calcium stores regulate plasma permeability for sodium.