Intraerythrocytic growth of the malaria parasite Plasmodium falciparum activates yet unidentified organic osmolyte and anion channels in the membrane of the human host erythrocyte. These channels deliver nutrients to the parasite, dispose of waste products, and counter-regulate the infection-induced swelling of the host cell (1). The parasite has been demonstrated to impose oxidative stress on its host erythrocyte which is produced during the digestion of the host hemoglobin (2). This oxidative stress seems to be involved in channel activation since reduced glutathione (but not oxidized glutathione) applied during whole-cell recording to the intracellular membrane face inactivates the channels in parasitized human erythrocytes. In addition, oxidation (1 mM t-butylhydroperoxide) of non-infected cells induces activation of identical channels (3). The channel activation upon oxidation or during infection is accompanied by ATP release from the erythrocyte. Moreover, purinoceptor antagonists or degradation of extracellular ATP by apyrase inhibit channel activation in oxidized or parasitized erythrocytes indicating autocrine purinergic signaling through P2Y1 receptor and further metabotropic purinoceptor subtypes (4). Accordingly, the organic osmolyte and anion channels activate delayed in oxidized or P. berghei-infected erythrocytes from P2Y1 knockout mice as compared to wildtype cells. In sharp contrast to oxidized or parasitized erythrocytes, extracellular ATP has no effect on channel activity in untreated control erythrocytes (4). The activation of the organic osmolyte and anion channels in oxidized or parasitized erythrocytes is paralleled by the activation of ClC-2 Cl-selective channels which contribute to the cell volume regulation of the parasitized erythrocyte. In addition, oxidation (1 mM t-butylhydroperoxide) and reduction (5 mM dithiothreitol) activates and inactivates ClC-2 heterologously expressed in Xenopus laevis oocytes, respectively (5). In summary, the increase in membrane permeability of malaria-infected human erythrocytes is probably induced by parasite-derived oxidative stress. Oxidation triggers ATP release-mediated purinergic signaling and activation of at least two different types of anion channels in the erythrocyte membrane.