Eighteen hours after intragastric inoculation Salmonella typhimurium elicited a net fluid secretion in the jejunum and ileum of rats. The mechanisms behind the secretory response were analysed in vivo. Extrinsic denervation of the experimental intestinal segments had no effect. The nerve-blocking agents hexamethonium (i.v.) and lidocaine (serosally applied) blocked the secretion but atropine had no effect. It was demonstrated that the bacteria were invasive by culturing from the intestinal wall. The presence of inflammatory reactions was supported by the facts that i.v. indomethacin blocked the secretory response and that there was an increased capillary leakage of albumin-bound Evans Blue into the interstitium of the intestinal mucosa. There was also a secretory response upon inoculation of the jejunal and ileal segments by cell-free supernatants of broth where bacteria had been cultured for 24 h and thereafter lysed. This response was, however, blocked by i.v. atropine, which had no effect on the secretion elicited by living bacteria. We could show no presence of E. coli LT, ST or cholera toxin in the cell-free supernatant by means of ELISA-tests. We therefore conclude that (1) S. typhimurium R5 invaded the rat jejunal and ileal mucosa, thereby creating an inflammatory response which in turn activated a nerve reflex(es) within the ENS leading to a net fluid secretion; (2) the presence of prostaglandins was needed for activating the reflex(es); (3) the reflex(es) contained a nicotinergic transmission; (4) enterotoxin was of no importance for the secretory response in the model used.