The asexual development of malaria parasites inside the erythrocyte is accompanied by changes in the composition, structure, and function of the host cell membrane and cytoplasm. The parasite exports a membrane network into the host cytoplasm and several proteins that are inserted into the erythrocyte membrane, although none of these proteins has been shown to have enzymatic activity. We report here that a functional malaria parasite-encoded vacuolar (V)-H ؉ -ATPase is exported to the erythrocyte and localized in membranous structures and in the plasma membrane of the infected erythrocyte. This localization was determined by separation of parasite and erythrocyte membranes and determination of enzyme marker activities and by immunofluorescence microscopy assays using antibodies against the B subunit of the malarial V-H ؉ -ATPase and erythrocyte (spectrins) and parasite (merozoite surface protein 1) markers. Our results suggest that this pump has a role in the maintenance of the intracellular pH (pH i ) of the infected erythrocyte. Our results also indicate that although the pH i maintained by the V-H ؉ -ATPase is important for maximum uptake of small metabolites at equilibrium, it does not appear to affect transport across the erythrocyte membrane and is, therefore, not involved in the previously described phenomenon of increased permeability of infected erythrocytes that is sensitive to chloride channel inhibitors (new permeation pathway). This constitutes the first report of the presence of a functional enzyme of parasite origin in the plasma membrane of its host.Plasmodium falciparum, one of the agents responsible for malaria, is an obligate intracellular parasite belonging to the phylum Apicomplexa. The asexual development of malaria parasites inside the erythrocyte is accompanied by changes in the composition, structure, and function of the host cell membrane and cytoplasm (1, 2). Upon invasion of the erythrocyte, the malaria parasite establishes a parasitophorous vacuole inside which it develops. In addition, the parasite interacts with its host cell and its environment by exporting a membrane network into the cytoplasm of its host cell and by inserting a number of proteins in the erythrocyte plasma membrane (3). As a result of these changes P. falciparum-infected erythrocytes show abnormally high permeability toward amino acids (1), sugars and polyols (2), purines (4), cations (5, 6), and anions (7,8). The mechanism responsible for this increased permeability has a strong preference for anions over cations and is blocked by drugs known to inhibit anion-selective channels (9). The increased permeability, therefore, appears to be the result of the parasite activating or inserting an anion-selective channel in the membrane of the erythrocytes (9). Electrophysiological evidence for the presence of an anionselective channel in the plasma membrane of P. falciparum-infected erythrocytes (10) supports this proposal (9). This channel has a high permeability to chloride ions, but it is not known whether it is encod...