The intestinal transmission of two macromolecular markers, of similar molecular weight but different susceptibility to proteolytic digestion, was investigated in the neonatal pig. Piglets of varying age (0 h-7 days old) were given a mixture of bovine serum albumin (BSA) and fluorescein-isothiocyanate labelled dextran 70,000 (FITC-D 70) by stomach tube, and the serum concentrations were determined 2 h after feeding. A high correlation between the patterns of transmission were obtained for the two marker substances (r=0.91, n=39). Furthermore, a rapid decrease in the transmission of the markers was observed during the first day of life in suckled piglets, and intestinal macromolecular closure was well developed in the piglets after 18-36 h of life. These findings indicate that 'closure' is unrelated to changes in intestinal proteolytic activity. After closure, only small amounts of the markers were transmitted to the serum. During the first day of life, great individual differences in the transmission were found between piglets. As shown by feeding different-sized FITC-D (MW = 3,000-70,000 dalton) and unconjugated FITC (MW = 389 dalton), molecules having a molecular weight greater than 3,000 daltons were excluded upon macromolecular closure. On the other hand, smaller molecules like FITC were transmitted across the intestinal barriers independent of closure.