The role of gastrin in regulating pancreatic growth and its interaction with secretin is unclear. We determined the dose-response relationships of pentagastrin for gastric and pancreatic secretion. Doses that stimulated gastric and pancreatic secretion were given every 8 h for 3 or 5 days; trophic responses of pancreas, oxyntic gland area, duodenum, and colon were compared. Interaction of secretin and pentagastrin on pancreatic growth was measured after 5 days of treatment. Pentagastrin was 250 times less potent for stimulation of pancreatic versus gastric secretion. A submaximal dose of pentagastrin for stimulating pancreatic enzyme secretion doubled pancreatic deoxyribonucleic acid synthesis after 3 days. Pentagastrin caused dose-related increases in pancreatic weight after 3 and 5 days. Pentagastrin had no effect on weight, deoxyribonucleic acid synthesis, or deoxyribonucleic acid content of oxyntic gland area, duodenum, or colon. Secretin had additive effects on pentagastrin-induced pancreatic growth. The pancreas appears to be more sensitive than other organs to trophic effects of pentagastrin. Secretin has additive rather than inhibitory effects on pentagastrin-induced pancreatic growth.