Wheat amylase inhibitor (WAI) was given to growing rats to determine whether chronic inhibition of intraluminal amylase activity alters pancreatic growth, pancreatic enzyme composition, and secretory responsiveness to cholecystokinin octapeptide (CCK-OP) and carbachol. For 21 days 13 rats were fed amylase inhibitor (AI) as 2.72% of the weight of their food; 13 were pair-fed controls (PFC), and 12 were controls with free access to food (FAC). Amylase and lipase secretion was measured from isolated pancreatic acini in response to CCK-OP (10(-12)-10(-8) M) and carbachol (10(-8)-10(-3) M). AI and PFC rats had similar food intakes and weight gains, pancreatic weights, and contents of enzymes (amylase, lipase, trypsin, chymotrypsin), protein, and RNA, but these measurements were significantly reduced compared to those of FAC rats. DNA contents per milligram of pancreas and per gram of body weight and amylase/DNA and trypsin/DNA were similar among all groups. Lipase/DNA and chymotrypsin/DNA in AI rats were the same as in PFC rats but significantly lower than in FAC rats. In response to CCK-OP, amylase secretion was similar in all three groups, but in response to carbachol amylase secretion was significantly less in AI compared to PFC and FAC rats. Lipase secretion increased in response to CCK-OP in AI compared to PFC and FAC rats but was similar in all three groups in response to carbachol. Long-term inhibition of intraluminal amylase activity suppresses pancreatic growth and content of enzymes and RNA by reducing food intake and weight gain and also decreases acinar cell secretion of amylase in response to carbachol and increases lipase secretion in response to CCK-OP.