This study was conducted to examine the relationship between soya-bean agglutinin and cholecystokinin in stimulating pancreatic enzyme synthesis in rats. In experiment 1, 30 rats were given daily gastric infusions of 0, 3·5, 7·0, 10·5, or 14·0 mg of soya-bean agglutinin (no.=6) for 14 days. Compared with the control group, soya-bean agglutinin reduced weight gains, enhanced absolute and relative dry pancreatic weights, elevated serum cholecystokinin levels, and stimulated cholecystokinin mRNA expression in the intestine (P<0·001). Pancreatic nucleic acid composition and the pancreatic activities of the enzymes amylase, trypsin and chymotrypsin all increased in response to increasing levels of soya-bean agglutinin (P<0·001). In experiment 2, duodenal cells obtained from two rats were incubated at 37°C with either saline, 100 μg/ml soya-bean agglutinin, or a mixture of 100 μg/ml soya-bean agglutinin and 10 mmol/m of the L-type, calcium channel antagonist verapamil. Soya-bean agglutinin stimulated cholecystokinin mRNA expression and cholecystokinin release from small intestinal mucosal cells, and the effect was attenuated by verapamil. In experiment 3, pancreatic acinar cells, obtained from three rats, were incubated at 37 °C with either saline, or cholecystokinin (100 fmol/ml) and soya-bean agglutinin (1000 fmol/ml), either alone or in combination. Amylase, trypsin, and chymotrypsin activities from both culture media and acini cells were stimulated by both the soya-bean agglutinin and the cholecystokinin treatments. Enzyme activities, when the two factors were incubated in combination, were intermediate to those obtained when the factors were incubated alone. This suggesting that soya-bean agglutinin may depress the action of cholecystokinin on pancreatic enzymatic activities. In summary, soya-bean agglutinin appears to stimulate pancreatic enzyme synthesis both directly and also through a cholecystokinin-mediated pathway.