The interaction between human transferrin and the transferrin binding proteins of Moraxella catarrhalis was studied by binding and affinity isolation experiments with transferrin and its derivatives. Competition binding experiments demonstrated that, compared to transferrin binding proteins in Neisseria meningitidis, the receptors in M. catarrhalis were more effectively blocked by iron-saturated transferrin than by the apo form of the protein. A combination of direct binding experiments and affinity isolation experiments demonstrated that this was due to a strong preference for binding of iron-saturated transferrin by transferrin binding protein 2 (Tbp2). Binding and affinity isolation studies also demonstrated that the C-lobe of human transferrin was fully capable of binding to M. catarrhalis transferrin binding protein 1 (Tbp1) but not to Tbp2. Neither the N-lobe nor a proteolytic derivative of human transferrin lacking only a portion of the C-terminus were capable of effectively binding to M. catarrhalis Tbp2, possibly implicating the involvement of several regions in the binding interaction.