Rabbit ileal loops were treated with purified Clostridium perfringens enterotoxin (CPE) to compare the onset of toxin-induced tissue damage with the onset of fluid transport changes (i.e. diarrhoea). Mild changes in fluid transport were detectable after 15 minutes of toxin treatment and then increased progressively with time. Histopathologic studies on toxin-treated ileal loops and measurement of toxin-treated loop fluid protein contents (an indirect marker for tissue damage) both indicated that detectable CPE-induced tissue damage also occurred within 15 minutes of toxin treatment and then progressively increased for at least the first 30 minutes of CPE treatment. Luminal fluid from CPE-treated loops contained elevated Ca2+ levels compared to control luminal fluid, but these elevated Ca2+ levels were not required to initiate in vivo CPE pathophysiologic effects. Since the onsets and severity of tissue damage and fluid transport changes coincided for at least the first 30 minutes of CPE treatment in our study, these results are consistent with CPE-induced tissue damage having a role in the initiation and extent of diarrhoea occurring during C. perfringens type A food poisoning.