The hythesis that a zinc-binding ligand (ZBL) recently discovered in human milk but absent from cow's milk might be related to zinc nutrition in the neonate was investigated. The zinc-binding characteristics of rat milk were examined to determine if the rat was a suitable model. By gel filtration, rat milk was found to contain a ZBL with characteristics similar to those of the ZBL found in human milk. A similar ZBL was identified in the intestinal mucosa of rats 16 days of age and older but was absent in rats from birth to 16 days. These results support the hypothesis that the ZBL of maternal milk may enhance zinc transport in the neonatal period before the development of intestinal mechanisms for zinc absorption. A recent report from this laboratory described the discovery in human milk of a low-molecular-weight zinc-binding ligand (ZBL) that is not present in cow's milk (1). We have proposed (1) that this ZBL is the factor responsible for the therapeutic value of human milk in the treatment of a genetic disorder of zinc metabolism, acrodermatitis enteropathica (AE), and that the ZBL acts by enhancing the absorption of zinc in patients suffering from this condition.AE is a hereditary disease in humans that appears in early infancy and is characterized by severe skin lesions, alopecia, and diarrhea (2). The onset of symptoms is frequently associated with the weaning of infants from breast milk to cow's milk (2-4). Without treatment, there is a relentless progression leading to death within I to 3 years (4). Since 1953, AE has been treated by oral administration of diiodohydroxyquin (Diodoquin) (5). Recently, Moynahan and Barnes (6) reported low plasma zinc levels in AE patients and successful treatment of the disorder with oral administration of zinc, the therapy resulting in an elevation of the plasma zinc and subsequent clearing of the epidermal lesions. The efficacy of zinc in the treatment of AE has been confirmed by other investigators (7,8). These findings indicate that the basic metabolic defect in this disorder is closely, if not directly, related to zinc metabolism, possibly at the level of zinc absorption as we proposed.We have also postulated that an intestinal ZBL necessary for zinc absorption is absent or immature at birth, even in normal individuals without AE, and that the ZBL of human milk may enable or enhance absorption of this element in the neonate until normal mechanisms of zinc absorption develop postnatally (9, 10). To test this hypothesis, we have used the rat as an experimental model. The present report describes the finding of a ZBL in rat milk similar to that present in human milk. In addition, the presence of a ZBL in the rat intestinal mucosa during the first few weeks of life was investigated.The costs of publication of this article were defrayed in part by the payment of page charges from funds made available to support the research which is the subject of the article. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely...