Previously, we reported that the phosphatidylcholine-specific phospholipase C (PC-PLC) inhibitor tricyclodecan-9-yl xanthogenate (D609) potentiates thapsigargin-induced Ca 2+ influx in human lymphocytes. In the present study we examined the effect of D609 on the thapsigargin-induced Na + entry. We found that the early phase of the thapsigargin-induced increase in the intracellular Na + concentration (approx. 1–2 min after stimulation) was attenuated after preincubation of lymphocytes with D609. By contrast, thapsigargin-induced Na + influx was not affected in the presence butan-1-ol, which inhibits phosphatidylcholine-specific phospholipase D (PC-PLD). The thapsigargin-induced Na + influx could be mimicked by PC-PLC exogenously added to the lymphocyte suspension, whereas addition of PC-PLD had no effect. In addition, thapsigargin stimulated formation of the physiological PC-PLC products, diacylglycerol. Cell-permeable diacylglycerol analogue, dioctanoyl-glycerol (DOG), produced time- and concentration-dependent increase in the intracellular Na + concentration. Both thapsigargin- and DOG-induced Na + increases were not affected in the presence of Na +/H + antiport inhibitor, HOE609, or Na +/Ca 2+ antiport inhibitor, dimethylthiourea, as well as in the presence of Co 2+ and Ni 2+, which block store-operated Ca 2+ entry. By contrast, markedly reduced thapsigargin- and DOG-induced Na + influx were noted in the presence of flufenamic acid, which blocks the non-selective cation current (I CRANC). In conclusion, our results suggest that diacylglycerol released due to the PC-PLC activation contributes to the thapsigargin-induced Na + entry.