Summary. The binding of iron‐saturated ¹²⁵I‐lactoferrin to human monocytes was studied at pH 7·4 and 37°C. Monocytes in suspension bound ¹²⁵I‐lactoferrin by a reversible, saturable and specific binding indicating the presence of a receptor. The dissociation constant (K_D) of the binding was estimated at about 4·5 × 10⁻⁹ M and the number of receptors was about 1·6 × 10⁶ per monocyte. The affinity of native lactoferrin (20% iron saturated) was only slightly below that of iron‐saturated lactoferrin (K_D about 7·9 × 10⁻⁹ M). Human transferrin, horse cytochrome c and human immunoglobulin G were without inhibitory effect on the binding of ¹²⁵I‐lactoferrin. The majority of cell‐bound ¹²⁵I‐lactoferrin was dissociable. The dissociation rate was not affected by addition of unlabelled lactoferrin to the dissociation medium. The binding of ¹²⁵I‐lactoferrin to adherent mononuclear blood cells showed an about 100‐fold lower affinity (K_D about 2·5 × 10⁻⁷ M) than to cells in suspension, but the specificity of the binding was the same. These results are compatible with the idea that lactoferrin exerts a biological effect mediated by an interaction with cells of the monocyte/macrophage lineage.