The effects of chlorpromazine (CPZ), berberine and verapamil on intestinal hypersecretion in the rabbit ileal loop model by the heat-labile enterotoxin (LT) of Escherichia coli were studied in relation to their ability to inhibit the stimulation of intestinal adenylate cyclase (AC) by LT. CPZ 5 mg by the intraluminal (i.1.) route and 4 mg/kg by the intramuscular (i.m.) route significantly reduced LT-induced intestinal hypersecretion. Berberine (10 mg) exerted an inhibitory effect, but only after i.1. administration, whereas verapamil did not exert any significant inhibitory effect when administered either i.1. (2.5 mg) or i.m. (4 mg/kg). At concentrations of (0.17-1.34) X 10(-3) M CPZ, the anti-secretory effect of CPZ correlated with its inhibitory effect on rabbit LT-stimulated intestinal AC. Inhibition of cAMP synthesis was probably not involved in the mechanism of action of the two other substances. These results indicate that CPZ and phenothiazines in general are efficient drugs for reducing LT-induced intestinal hypersecretion and could represent a model for synthesis of new anti-secretory drugs with no tranquiliser side effects.