The physiological changes following the reaction of lead upon red blood cells are numerous and show the marked effects of a change in the cell surface. In experiments here reported 0.01 to 0.05 mg. of lead acting upon 5 billion red cells caused such marked variations from normal as: 1. Partial loss of the normal stickiness of red corpuscles, which is demonstrated by their falling from a clean glass surface. 2. Loss of the agglutination reaction which normally follows mixture with serum of a different isoagglutinating group. 3. Decrease in volume even in isotonic solutions. 4. Loss of normal elasticity and, therefore, reduced changes in volume upon exposure to marked variations in osmotic tension. 5. Increase in resistance to large changes in external osmotic pressure because of this inelasticity, and therefore decreased hemolysis in hypotonic salt solution (Part 1). 6. Increase in the speed of disintegration in spite of this increased resistance to external osmotic pressure. "Leaded" cells break up more readily upon standing than do normal cells, and are easily fractured by rotation or shaking (Part 1). All these phenomena seem to be associated largely with surface changes in the corpuscles. Evidence is cited that there is no chemical reaction between lead and hemoglobin. The gas exchange is identical in normal and "leaded" cells. The function of the interior of the red cells, therefore, appears to be unaffected by lead. The effects of lead upon red blood cells are thus manifested by shrinkage, inability to expand, increased brittleness, and loss of the normal consistency which makes their surface sticky. After exposure to lead, red blood corpuscles are more like hard inelastic brittle rubber balls, than like the soft, elastic, resilient cells characteristic of normal blood.