Small quantities of iron bound specifically to human transferrin were found to stimulate infection with Neisseria meningitidis strain M1011 in mice. An intraperitoneal injection of 17.5 mg of transferrin carrying 22.7 micrograms of Fe resulted in 100% mortality from infection, as compared with no mortality for the controls which had received saline. Five milligrams of ferri-transferrin (FeTf), carrying 6.5 micrograms of Fe, stimulated and prolonged bacteremia in the mice. Thus, FeTf maintained infection, whereas infection was controlled due to iron limitation in control mice. Comparative studies with apotransferrin (iron-free) revealed that the enhancement of infection was due to the supply of iron. FeTf was also found to relieve an iron limitation of growth achieved by ethylenediaminedihydroxyphenylacetic acid (EDDA) in vitro. FeTf abolished the lag phase for growth of N. meningitidis in a defined medium. The results of this study suggest that human FeTf is an immediate source of iron to N. meningitidis both in vitro and in vivo. These findings support the hypothesis that the levels of iron in the circulating transferrin pool of mice determine the course of experimental N. meningitidis infection.