Human milk contains non-immunological factors that provide protection against infectious organisms. Two milk glycoproteins have been identified that have inhibitory activity, the milk MUC-1 mucin and lactadherin. The milk mucin has been shown to bind specifically to S-fimbriated E coli and inhibit binding of this organism to baccal epithelial cells. Lactadherin has been implicated in the prevention of rotavirus-induced diarrhea in breast-fed infants. Also, glycosaminoglycans have been found to inhibit HIV glycoprotein gp 120 binding to its host cell CD4 receptor. Both the milk mucin and lactadherin are major components of the human milk fat globule, and survive in the stomach of human mild-fed infants and most likely reach significant levels in the intestinal tract. The milk mucin is detected in the stool of human milk-fed infants. The milk mucin is a polymorphic, large molecular weight, and highly O-linked glycosylated glycoprotein. Its cDNA derived amino acid sequence contains a large central domain consisting of a variable number of 20 amino acid tandern repeats, an N-terminal domain with a signal sequence and a C-terminal domain containing a hydrophobic transmembrane region. Lactadherin is a 46 kDa, membrane-associated cell adhesion molecule that binds to integrins. Its anti-rotaviral activity may involve direct interaction with the virus or lactadherin may also act indirectly by enhancing the development of the intestinal mucosa. The active anti-HIV glycosaminoglycan appears to the either chondriotin sulfate or a chondriotin sulfate-like moiety. The importance of non-immunological factors in human milk on prevention of infection in newborn infants will be discussed and clinical data on the role of these non-immunological factors will be reviewed. Also, the structure of these glycoproteins will be discussed and related to possible mechanisms of action.