ABSTRACT V-ATPases in phagocytic cells are known to mediate the acidification of most intracellular organelles. Proton-pump-mediated acidification of these organellar compartments is vital to numerous cell processes, including receptor recycling, protein processing and sorting and microbial degradation. Recent studies have suggested a role for V-ATPases in cytoplasmic pH homeostasis. The present discussion will review the current knowledge regarding the presence of V-ATPases in both the plasmalemmal and organellar membranes of phagocytic cells, the regulation of proton pump activity in these locations and the functional significance of pump-mediated proton translocation.