Jejunal perfusion was performed in 12 healthy volunteers to evaluate the dose dependent effects of loperamide on intestinal absorption, stimulated secretion and transit. In 6 volunteers intestinal perfusion of the jejunal segment with isotonic NaCl solution was followed by addition of loperamide in increasing doses (2-8 mg.l-1). The volunteers were pretreated with 1 mg.l-1 prostaglandin E2 (PgE2) in the perfusate before addition of 4 mg.l-1 loperamide. Phenolsulphonphtalein (PSP) boluses (2 ml) were given to measure mean transit time (MTT). Loperamide 2 mg.l-1 converted the minor secretion after perfusion with the standard solution (water -145 ml.min-1, Na -0.09 and Cl -0.04 mmol.min-1) to absorption (water 0.93 ml.min-1, Na 0.23, Cl 0.25 mmol.min-1) within 15 min. Higher doses of loperamide did not increase absorption. The addition of PgE2 induced net secretion of water (-4.48 ml.min-1) and electrolytes (Na -0.57, Cl -0.51 mmol.min-1). Loperamide 4 mg.l-1 significantly diminished the PgE2-induced net secretion by approximately 50%. Loperamide dose dependently increased the MTT from 6 (2 mg.l-1) to 13.3 min (8 mg.l-1). MTT was still delayed 60 min after a wash out period (10.5 min). It is concluded that loperamide had a dual effect or intestinal activities stimulating absorption and prolonging intestinal transit time with rising doses.