1. The entry of [125I]polyvinyl pyrrolidone (PVP) of mean mol. wt. 160,000 (K. 60) into the epithelial cells of the small intestine has been measured in new‐born animals of five species. 2. The distribution along the intestine of cells capable of taking up [125I]PVP and the decrease and eventual cessation of uptake (closure) with increasing age have been investigated, and have been related to changes in the histological appearance of the small intestine. 3. The small intestine of the ferret took up PVP readily until 33–34 days after birth. From 34 to 37 days of age PVP uptake declined sharply and disappeared completely by 40–45 days. 4. in the ferret, unlike other species studied, some PVP was taken up by the duodenum. This continued for the first 4 weeks after birth. Thereafter PVP uptake gradually became confined to the terminal ileum. 5. in the guinea‐pig, PVP uptake was limited to the first 48 hr after birth. During this period the site of uptake was progressively restricted to the terminal ileum. 6. in the rabbit, PVP could be taken up in the distal two‐thirds of the small intestine for at least 20 days after birth. A decline in uptake occurred between 20 and 22 days after birth in most animals. 7. Wide individual variations were seen in the kitten, but PVP uptake was seen in some animals up to 14 days after birth. 8. Newly hatched chicks and chicks tested 48 hr after hatching did not take up PVP. 9. Histological examination of the small intestine with the light microscope demonstrated that in all species PVP uptake was associated with the presence of vacuoles in the epithelial cells of the villus. 10. in the young guinea‐pig, large PAS‐positive granules were seen in the macrophages of the lamina propria. These appeared to migrate through the epithelium into the intestinal lumen. The significance of this finding and its relation to macromolecular uptake remain unclear.