1. 5-HT increased the electrical activity of rat jejunum both in vivo and in vitro. The increased potential difference and short-circuit current resulted from a stimulation of electrogenic chloride secretion. NaCl absorption may also have been inhibited. 2. 5-HT did not alter cyclic AMP levels in isolated enterocytes. 3. The 5-HT response in vivo was unaffected by atropine, cyproheptadine, propranolol and hexamethonium. Phenoxybenzamine reduced the maximum response without affecting the dose required to produce a 50% maximum response. Methysergide, at a dose of 40 mg/kg, had a similar effect while a lower dose of 2 mg/kg produced no change. Mianserin competitively antagonized the response to 5-HT, a dose of 2 mg/kg producing a fourfold increase in the amount of 5-HT required to produce a 50% maximum response. 4. Acetylcholine and 5-HT seem to act independently in inducing intestinal secretion since atropine did not block the response to 5-HT and Mianserin did not alter the response to acetylcholine. 5. Experiments in which the intestinal villi or crypts were subjected to preferential damage suggested that 5-HT primarily produced its response at the crypt cell level.