Understanding the differences between the protein system of human milk and bovine milk is critical in the development of infant formulae. In this study, the proteins of bovine milk and a bovine-based whey-dominant infant formula were compared with those of human milk for infants born prematurely (pre-term) or at full term (term). The protein distribution of infant formula differed significantly from that of either type of human milk. A proteomic comparison between pre-term and term human milk showed a reduction of levels of beta-casein and alpha(s)-casein and appearance of additional products, corresponding to low molecular weight hydrolysis products of the caseins, in pre-term milk. Pre-term milk samples also had higher total nitrogen concentration and plasmin activity, consistent with the proteomic data. These results suggest the operation of a physiological mechanism that may adjust enzyme and/or protein expression to modify protein digestibility, and may facilitate design of infant formulae, closer to maternal milk, particularly for premature infants. (C) 2010 Elsevier Ltd. All rights reserved.