To determine how low or high dose of caerulein, a cholecystokinin analogue influence pancreatic growth, doses of caerulein were selected which were submaximal (1 microgram/kg i.p.) and supramaximal (10 micrograms/kg i.p.) for enzyme protein secretion. Rats were injected every 8 h for 7 days with saline, low, or high dose of caerulein. The low dose of caerulein significantly increased pancreatic weight and content of DNA, protein, and digestive enzymes. The high dose caerulein group did not differ from control in these parameters of pancreatic growth. The number of zymogen granules was increased in both caerulein-treated groups. However, zymogen granules in the high dose group were atypical, appearing lucent or having a dense core with a lucent halo. These results indicate that caerulein has a biphasic effect on both enzyme secretion and the trophic response of acinar cells, and that the inhibitory effect of high dose of caerulein on pancreatic growth is accompanied by alterations in acinar cell morphology.