An experimental model was established using the terminal ileum of the rat for characterizing and studying the effects of crude cell-free extract from Clostridium perfringens upon physiological and histological parameters involved in the transport process. Further work was done with the model system using purified enterotoxin (protein) from the cell extract. Using an in vivo perfusion technique it was found that crude extract induces a reversal of net transport, from absorption in controls to secretion, of water, sodium, and chloride. Glucose absorption was greatly inhibited, whereas potassium and bicarbonate transports were unaffected. Crude extract also caused histological damage to the villus epithelium by denuding the villus tips, thereby leaving the lamina propria exposed. Similar responses in transport of water, sodium, chloride, bicarbonate, and glucose were caused by purified toxin. Little or no histological damage resulted from the pure toxin activity. However, the toxin was shown to have the capacity to denude villus tips under the proper experimental conditions.