Membrane transport--sodium (Na+) influx and calcium (Ca2+) uptake--was examined in human mature red cells treated with phospholipase A2 (PLase A2) from snake venom. PLase A2-induced conversion of phosphatidyl choline (PC) to lysophosphatidyl choline (L-PC) was associated with a marked increase in Na+ influx and Ca2+ uptake. After L-PC was removed from the cell membrane of the PLase A2-treated red cells in the presence of albumin, an additional increase in Ca2+ transport was observed. These results indicate that membrane lipid abnormalities, such as increased L-PC and/or a loss of total lipids, appear to induce increased membrane transport.