Abstract 1. The anemia produced by lead intoxication in humans as well as experimentally induced lead poisoning in dogs results in a positive direct Coombs test. 2. The direct antiglobulin test will become positive within twenty-four hours in cases of severe lead poisoning produced experimentally in dogs. 3. The blood from cases of severe lead poisoning in dogs will form a layer phenomenon when allowed to stand with the formation of a supernatant fraction of cells above the packed erythrocytes. These cells remain suspended in the plasma for many hours. This superior fraction on a column of blood has a high per cent of reticulocytes, and cells with coarse basophilic stippling. The direct Coombs test is positive in the superior fraction of such a column. The positivity decreases as the sampling approaches the bottom. In many instances the whole blood direct Coombs test may be negative and the cells from the superior portion of the column be strongly positive. The latter phenomenon was also found in asymptomatic workers exposed to lead in a smelting plant. 4. The possible significance of the correlation of the direct anti-globulin reaction and cell immaturity or chemical trauma to the membrane is briefly discussed.