Intraluminal perfusion with Escherichia coli heat-stable enterotoxin (ST) reversed water and electrolyte movements from net absorption to net secretion in porcine jejunal segments. Addition of berberine hydrochloride (3.2 X 10(-5) M) to the perfusate reduced the jejunal secretory response of water, sodium, potassium, and chloride to ST and enhanced water and electrolyte absorption in control segments. At lower concentrations (1.1 X 10(-5) M), berberine reduced the secretory response in ST-exposed segments, but only the decrease of sodium flux was significant. In the presence of berberine, the mucosal enzyme activities of adenosine triphosphatase and disaccharidases were not significantly different between control and ST-exposed segments. Doses of 1, 2, 3, 4, 5, and 10 mg of berberine were injected into ligated loops of proximal part of the jejunum with 1 ml of ST filtrate. At doses of 2 or more mg/loop, berberine was effective in reducing water and electrolyte secretions induced by ST; the effect was dose-dependent. These findings indicate that berberine may be an effective antidiarrheal agent in E coli heat-stable enterotoxin mediated secretory diarrhea and provide a basis for the frequent empirical use of berberine alkaloid and berberine-containing plants in gastroenteritis and infectious diarrhea in Asian and other countries.