A study, using the piglet as a model for the human infant, was undertaken to determine the effect of the protein source of a milk formula on organ development, the activity of digestive enzymes, and the absorption of amino acids as measured at the terminal ileum and over the entire digestive tract. Three isocaloric liquid milk formulas containing equal amounts of either intact bovine milk, hydrolyzed bovine milk, or isolated soybean protein as the sole source of this nutrient and with equal levels of fat and carbohydrate were each given to six 14-day-old piglets over a 19-day period in a manner that mimicked human infant feeding practice. Following a 6-day metabolism study, the piglets were killed, their organs removed, and samples of digesta collected. The protein source of the milk-based formula did not affect (p greater than 0.05) the weight/unit body weight of the small intestine, large intestine, liver, or pancreas, but the relative weight of the kidneys was lower (p less than 0.05) for animals fed the intact bovine milk-based formula and that of the stomach was higher (p less than 0.01) for piglets receiving the isolated soybean formula. The activities of pepsin, intestinal trypsin and chymotrypsin and pancreatic chymotrypsin were not influenced (p greater than 0.05) by protein source, but piglets receiving the bovine milk-based formula had a lower level of activity (p less than 0.01) for pancreatic trypsin. The apparent ileal and fecal absorption of nitrogen was similar for the three milk-based formulas, the overall mean ileal absorption of nitrogen (+/- SE) being 89.0% (+/- 1.44). Excluding cystine, where ileal absorption was relatively lower (p less than 0.05) with the isolated soybean formula (86.7%) compared with the intact bovine milk (91.5%), protein source had little effect on the apparent absorption of essential amino acids. It was concluded that the replacement of intact cow's milk protein in human infant formulas by either hydrolyzed cow's milk or isolated soybean protein is unlikely to cause any major disturbance in the digestive process.