An isolated sac of rat upper small intestine was prepared. Its lower end was drained to the skin. Solutions of known volume and composition were infused into the sac and the intestinal mucosa was examined by light and electron microscopy. Infusion of isosmotic (16.8% w/v) polyethylene glycol (PEG) resulted in prompt and progressively severe damage to enterocytes at the top of the villus, while goblet cells and basal-granulated cells were apparently unaffected. Thus, after 6-72hrs a cap of goblet cells and basal-granulated cells accumulated at the tip of the villus, while the enterocytes underwent vacuolation and disintegration. Infusion of an isosmotic mixture of 1% PEG and 5.1% glucose caused no damage near the site of infusion, but damaged the intestinal sac further distally. The infusion of distilled water also damaged enterocytes, but the pattern of damage was different from that seen with PEG. Infusion of isosmotic glucose solution appeared to cause no damage to the mucosa. The damage caused by PEG infusion had disappeared 6hrs after the replacement of PEG by an infusion of isosmotic glucose solution. These results were discussed in reference to the turnover and kinetics of the intestinal epithelium.