In 2 cases of chronic hemolytic anemia with erythrocyte fragility to cold and acid, although the abnormality resides in the red blood cells, serum, whether from the patients or from normal controls, is necessary for the hemolysis.

Complement is most likely not responsible for the serum hemolytic activity, because the latter, while similar to complement in certain properties, may be completely dissociated from it.

From human serum the euglobulin separated by CO2 and sodium sulphate and the pseudoglobulin I obtained by sodium sulphate precipitation possess hemolytic activity for the cells of the patient and not those of the control. The hemolytic activity of these globulin fractions is increased by chilling and by addition of acid. It is inhibited by serum pseudoglobulin II and albumin.

Guinea pig serum aids human serum in its hemolytic activity on susceptible human cells. This augmenting effect of the guinea pig serum is not due to its complement content, nor due to its hetero-hemolysin for all human erythrocyte.

In view of the data presented in this and the preceding papers, a new syndrome is suggested which can be clearly differentiated from paroxysmal cold hemoglobinuria and from paroxysmal nocturnal hemoglobinuria.

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