The effects of various pharmacological agents on bile acid-induced fluid secretion, mucus secretion, and mucosal injury were investigated using a perfusion technique in rabbit colon. Atropine markedly reduced and carbachol potentiated the fluid secretion, mucus output, and mucosal damage observed during bile acid perfusion. In contrast, pretreatment of the colonic mucosa with lignocaine and parenteral administration of methysergide and somatostatin produced a modest reduction in the fluid secretory response without apparent effects on mucus output or mucosal damage. These results suggested that cholinergic agonists and antagonists influence the mucosal resistance to bile acid-induced injury possibly through their effects on mucus secretion. Increasing or decreasing mucosal resistance to the detergent effects of bile acids appeared to have marked effects on the magnitude of induced fluid secretion. A minor reduction in overall secretory response to bile acids was also apparent with agents not influencing mucus secretion or mucosal injury.