We previously showed that soybean lectin (SBL) releases cholecystokinin (CCK) and have now asked whether other dietary lectins have this effect and if extracellular calcium is involved. Lectins and vehicle were first infused into the duodenum of anesthetized rats. The CCK response to vehicle was 3.1 ± 0.6 pmol/l (P < 0.05 vs. basal). SBL and peanut lectin (PNL) (84 µg/ml) significantly increased plasma CCK concentrations from 2.0 ± 0.4 pmol/l to a maximum of 8.4 ± 0.5 pmol/l (P < 0.01 vs. vehicle, mean ± SE) and from 1.9 ± 0.5 to 7.0 ± 0.6 pmol/l (P < 0.05 vs. vehicle, mean ± SE), respectively. Wheat germ lectin (WGL) (840 µg) also increased plasma CCK levels from 1.5 ± 0.3 pmol/l to a maximum of 9.7 ± 1.3 pmol/l (P < 0.05 vs. vehicle, mean ± SE). Corresponding increases in pancreatic protein output occurred. Broad bean lectin (BBL) had no effect on either parameter. Dose-dependent responses were seen with SBL, PNL, and WGL (1, 10, and 100 µg/ml) in perifused rat intestinal cells. These responses were abolished in calcium-free medium and in the presence of the competing sugars of the lectins. Therefore, SBL, PNL, and WGL, which bind to motifs including N-acetyl-D-galactosamine, galactose, and N-acetylglucosamine, respectively, released CCK, but BBL, which binds to mannose and glucose, did not. Ingestion of lectins may have major CCK-mediated effects on gastrointestinal function and growth.