The percentage of complement-sensitive erythrocytes varies among patients with paroxysmal nocturnal hemoglobinuria (PNH) and is related to disease severity. We examined the changes of complement-sensitive erythrocytes following administration of androgens, prednisolone, dextran, and iron to 12 PNH patients using the complement lysis sensitivity test or flow cytometric analysis of decay accelerating factor and CD59/membrane attack complex-inhibitory factor expression for 11 years. Five untreated PNH patients were also studied as a control group. The complement-sensitive erythrocyte count remained almost constant in the control group, while it increased in four out of five patients receiving androgens. In addition, it decreased in two out of three patients receiving prednisolone, increased in both patients treated with dextran, and increased slightly in two of the three patients receiving iron therapy. Episodes of hemoglobinuria increased in three of the nine patients showing an increase of complement-sensitive erythrocytes, and decreased in four patients receiving prednisolone or dextran. A good response to treatment was clinically observed in four patients receiving androgens, in one patient treated with prednisolone, and in one patient receiving dextran according to the scoring system. These findings suggest that PNH remains stable when the number of complement-sensitive erythrocytes remains fairly constant, and that the PNH III erythrocyte count is especially related to the frequency of hemoglobinuria. Thus, it seems to be important to determine the long-term effect of drug therapy on complement-sensitive erythrocytes to select the most appropriate treatment.