ABSTRACr The addition of lead to normal human blood was previously found to cause a decrease in erythrocyte osmotic fragility in vitro. The mechanism of the decreased osmotic fragility caused by lead has not been completely clarified, but the following hypothesis has been proposed. Lead causes a leakage of water from erythrocytes, thus more water can enter the cell before haemolysis occurs. There has been no report, however, of the direct measurement of the intracellular water content of erythrocytes treated with lead. This study has tried to clarify the relation between intracellular water and the osmotic fragility of lead-treated erythrocytes in vitro. The results showed that 0.05 ,uM/ml of lead decreased the osmotic fragility, the intracellular water content, and intracellular potassium and mean corpuscular volume, increased the plasma water content and trapped water content, and contracted the erythrocyte shape. These changes corresponded well with each other, and close coincidence of the osmotic fragility and the intracellular water content was also observed.In previous papers'2 we observed a decreased erythrocyte osmotic fragility in workers occupationally exposed to lead compared with controls and found a dose-response relationship between the blood lead concentrations and the osmotic fragility in lead workers using the coil planet centrifuge (CPC) method.3 We also observed, by an in vitro experiment,4 that the addition of lead to normal human blood caused a decrease in the osmotic fragility using the CPC method.The exact mechanism of the decreased osmotic fragility is not completely understood, but the following hypothesis has been generally accepted. The addition of lead to blood causes a leakage of potassium accompanying water from the erythrocytes, which means that more water can enter the cell before haemolysis occurs.5 There has been no report, however, of the direct measurement of the intracellular water content of erythrocytes treated with lead. We