Lectins are daily ingested plant proteins resistant to proteolytic degradation and survive the passage through the GI tract in a biologically active form. By binding to glycosyl side chains of receptors they can mimic ligands. The lectin phytohaemagglutinin (PHA) potently releases cholecystokinin (CCK) in rats. Since the effects of PHA on CCK-mediated functions in man are unknown we investigated the effect of intraduodenal (id) administration of PHA on plasma CCK levels and gallbladder (GB) contraction. Five healthy volunteers underwent 4 studies on different days. After a basal period of 30 min with id saline, PHA was infused in increasing doses: 150 mg, 1.5 mg, 15 mg, 30 min each dose. The following treatments were administered in random order: 1)iv saline 2)heat-inactivated PHA 3)iv atropine 4)iv dexloxiglumide. CCK levels were determined with RIA. Gallbladder volumes (GBV) were measured by ultrasonography. PHA induced GB contraction in a dose-dependent manner starting at the lowest dose of PHA (64 ± 9 % of basal GBV). Heat-inactivated PHA or atropine did not affect GBV (106 ± 9 % and 108 ± 8 % of basal GBV, respectively). Blocking CCK-A receptors with dexloxiglumide abolished PHA induced GB contraction (208 ± 23 % of basal GBV). Plasma CCK levels were not affected by any treatment. Dietary administration of the lectin PHA potently stimulates GB contraction in man without affecting peripheral plasma CCK levels. Blocking CCK-A or muscarinic receptors completely abolished PHA-stimulated GB contraction. In contrast to free fatty acids or amino acids mediating GB contraction predominantly by plasma CCK release, PHA seems to involve CCK-A and muscarinic receptors along neuroendocrine pathways. Therapeutic potential of lectins during prolonged total parenteral nutrition remains to be determined.