Intestinal macromolecular transmission in young rats of 10, 14, 18, 22 and 30 days of age was measured as the blood serum levels of markers 6 h after oral feeding of a solution containing bovine IgG (BIgG), bovine serum albumin (BSA) and fluorescein-isothiocyanate-labeled dextran 70,000 (FITC-D), either alone (controls) or with soybean trypsin inhibitor (SBTI) or swine colostrum trypsin inhibitor (SCTI). In the 10- and 14-day-old rats, transmission of all three macromolecular markers was high, with a preference for IgG. Transmission was greatly reduced by the age of 18 days and totally arrested for the protein markers at 22 days, with a low transmission of FITC-D remaining at 30 days of age. Addition of either of the two protease inhibitors significantly elevated the transmission of the protein markers in the rats aged 10, 14 and 18 days, while the transmission of the protease-independent marker FITC-D was unaffected. From 14 days of age, the rats have a functioning intestinal proteolysis, since only small amounts of marker proteins were left in the gut lumen 6 h after feeding, and since the addition of protease inhibitors resulted in increased amounts of undegraded proteins intraluminally. The results indicate that the increase of intraluminal proteolytic activity during development and the presence of protease inhibitors in the food are of importance for the intestinal transmission of undegraded proteins in the young rat. The Fc receptor for IgG in the enterocyte is not sufficient to maintain an optimal transmission of IgG, since the intraluminal proteolytic activity also appears to be of importance.