Staphylococcus aureus is able to utilize efficiently transferrin-bound iron as an iron source, whereas other staphylococci are not. The reason for this difference remains unclear. We compared the activity of siderophore-mediated iron-uptake systems among S. aureus, S. epidermidis, and S. saprophyticus. S. aureus was more susceptible to streptonigrin than the other two staphylococci. S. aureus was able to utilize efficiently transferrin-bound iron in proportion to the level of iron-saturation and produced siderophores in an inverse relation to iron-saturation. In contrast to S. aureus, S. epidermidis and S. saprophyticus were able to utilize only holotransferrin (HT; about 80% iron-saturated) and produced siderophores only in media containing HT. Moreover, they utilized HT less efficiently than S. aureus, though they produced greater amount of siderophores than S. aureus in media containing HT. The ability of the equivalent siderophores per se to capture iron from HT was not significantly different among the three species. Nevertheless, the siderophores from S. aureus stimulated the growth of the staphylococci to a greater degree than did the siderophores from S. epidermidis and S. saprophyticus. The siderophores from S. epidermidis and S. saprophyticus also stimulated the growth of S. aureus to a greater degree than those of the original bacteria which produced them. This indicates that S. aureus possesses a greater ability to produce more-efficient siderophores responding to very low iron-availability, as well as a greater ability to utilize iron-siderophore complexes, than the other two staphylococci. This explains in part the higher virulence of S. sureus compared to other staphylococci.