We studied the macromolecular permeability of segments of jejunum from 2-wk-old piglets after the animals had been experimentally infected with an invasive enteric virus , transmissible gastroenteritis virus. Jejunal segments were mounted in Ussing chambers at stages of the infection, and permeability was measured using three probe molecules of differing molecular weights. In control tissue, permeability to horseradish peroxidase was 2.6 times higher across segments with Peyer's patches than across segments without Peyer's patches, whereas polyethylene glycol 4000 and mannitol permeabilities were the same in patch and nonpatch segments. Twelve hours after infection, when virus had invaded the mucosa causing a structural lesion, and before diarrhea had begun, horseradish peroxidase permeability increased in non-patch-containing segments to equal that across patch-containing tissue. At this early 12-h stage, polyethylene glycol 4000 and mannitol permeation were unchanged in patchcontaining segments compared with controls. Ninety-six hours after transmissible gastroenteritis infection, when diarrhea was severe, horseradish peroxidase permeability in patch-free segments had