Decay-accelerating factor (DAF) is a 70,000 Mr membrane protein that inhibits the amplification of the complement cascade on cell surfaces. Monoclonal antibodies against different epitopes of the 70,000 Mr DAF (DAF-1) recognize a second band at the position of 140,000 Mr on a Western blot of total red cell ghost proteins or partially pure DAF subjected to electrophoresis under denaturing conditions. Like DAF-1, this polypeptide (DAF-2) has the ability to accelerate decay of the C3 convertase, C4b2a, and to reincorporate into red cell membranes. A population of erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) lack DAF-1 and also DAF-2. In addition, in some patients' red cells bearing DAF-1 of normal Mr, DAF-2 is 5,000 to 10,000 Mr smaller than normal. The structural basis for these differences in size of DAF and its PNH variants is unknown.