In order to elucidate the action mechanism of dapsone on blood cell membranes, we assessed the dose-dependent effect of dapsone on the activities of choline phosphotransferase (which mediates the production of the structural phospholipid, phosphatidylcholine) and methyltransferase (which produces phosphatidylcholine from phosphatidylethanolamine, representing the dynamics of the cells) in the membranes of red cells, lymphocytes, and neutrophils obtained from 16 healthy human subjects. The methyltransferase activity of lymphocyte and neutrophil cell membranes was slightly inhibited by dapsone, although only at a high concentration (1 mM), while that of red cells was not affected. On the other hand, dapsone significantly decreased the choline-phosphotransferase activity of red-cell membranes in a dose-dependent fashion, but did not significantly inhibit that of lymphocytes or neutrophils. The mechanisms of the hemolytic side effect of dapsone on erythrocytes and its anti-inflammatory effect on neutrophils are discussed in connection with its inhibitory effect on the enzymatic activities of membrane phospholipids.