The binding of cytochrome c to phospholipid vesicles was studied by the ultracentrifugation method as a function of pH and ionic strength in order to correlate the binding properties with membrane fusogenic properties of this protein. The pH dependent binding profile of the cytochrome c is complicated showing binding maxima around pH3 and pH9. Appreciable binding persistes even at high ionic strength and the binding reaction is partially irreversible indicating the involvement of hydrophobic interaction. The cytochrome c induced fusion of phospholipid vesicles, as observed by the intermixing of vesicles contents, also shows a complicated pattern. Above pH7, there is a fusion maximum at around 9. Below pH7, however, the extent of fusion increases steadily with decreasing pH. The relationship between the binding of cytochrome c to vesicles and the cytochrome c induced fusion of vesicles is discussed in terms of hydrophobic interaction between this protein and vesicles.