Intracellular-free calcium concentrations were measured in the intestinal epithelial cells isolated from the rabbit ileum treated with Shigella dysenteriae type 1 toxin. There is almost a five-fold increase in the [Ca+2]i levels in the epithelial cells isolated from the toxin-treated rabbit ileum compared to control. The [Ca+2]i levels were also measured in the presence or absence of tetrodotoxin, a neurotoxin, and atropine, a muscarinic cholinergic antagonist. These drugs significantly decreased the [Ca+2]i levels of the cells isolated from the toxin-treated rabbit ileum. Furthermore, the unidirectional fluxes of Na+ and Cl- were determined in both the S. dysenteriae type 1 toxin-treated and control rabbit ileum. Dantrolene significantly stimulated net absorption of these ions in the toxin-treated ileum, suggesting the involvement of [Ca+2]i in the regulation of intestinal electrolyte transport. To evaluate the role of neural mechanisms, the transport of these ions was also determined in the presence and absence of tetrodotoxin and atropine. The presence of these drugs caused significant absorption of Na+ and Cl- in the toxin-treated compared to their absence. These findings suggest that the enteric nervous system plays an important role in S. dysenteriae type 1 toxin-induced diarrhoea, and the release of neurotransmitters causes changes in the intracellular calcium levels, ultimately changing electrolyte transport across the rabbit ileum.