The iron-binding proteins transferrin and lactoferrin restrict the amount of ionic iron available in body fluids to 10(-18) M. This amount is insufficient for normal bacterial growth, and pathogens acquire iron either by producing iron-chelating agents or by utilizing heme compounds. Iron-binding proteins, in combination with antibodies, often have powerful bacteriostatic effects in vitro and are essential for protection against many infections. Lactoferrin appears to be essential for the bactericidal function of polymorphonuclear leukocytes against Pseudomonas aeruginosa. Fever lowers the concentration of iron in serum and favors resistance to infection. Liberation of heme compounds can enhance clinical infections.