We have defined by using competition experiments the nature of specific lactoferrin binding sites, probably responsible for the previously observed stimulatory growth effect of the iron binding protein on HT29-D4 cells. Lysozyme, albumin and fucose do not affect lactoferrin binding showing that the binding of the protein is mediated neither by electrostatic forces nor by fucose. Iron-free and iron-loaded protein produce similar effects, demonstrating that the metal is not involved in the protein recognition. Similar results are observed for transferrin. A specific binding inhibition of lactoferrin by cathepsin G, a leukocyte proteinase, is observed, suggesting the existence of a common receptor for lactoferrin and cathepsin G on HT29-D4 cells. These results and the fact that tumor tissues are more often infiltrated by inflammatory cells such as polymorphonuclear leukocytes could evoke an unexpected role for leukocytes, possibly mediated in part by these two proteins, on the proliferative cancer effect.