The effects of a Shiga toxin derived from Shigella dysenteriae Type 1, Strain 60R, and a Shiga-like toxin from the enterohemorrhagic Escherichia coli O157:H7, Strain 933, were studied in the in vivo rabbit ileal loop model. The effects of both toxins were similar and resulted in severe villus blunting by 18-24 hours after exposure. With both toxins, a dose effect was noted; and the lesions, first detected at 2 hours after inoculation, became more severe over time. Both toxins appeared to act directly and selectively on the mature columnar absorptive epithelium of the intestinal villus, which resulted in the premature expulsion of these cells from the lateral villus wall, with a decrease in the villus/crypt ratio. The goblet mucous cells remained attached and frequently formed clusters on the blunt villus apices. The crypt epithelium underwent a rapid proliferation and maintained the epithelial integrity. The ultrastructural changes observed in the toxin-injured villus absorptive cells suggested that these cells underwent a process of apoptosis, rather than necrosis. These findings suggest that both toxins act in vivo in the small intestine on a specific cell population, the mature, differentiated absorptive villus epithelium.