This study was designed to compare, on a molar basis, the effect of chronic bombesin, gastrin-releasing peptide (GRP) and caerulein on pancreatic growth in the rat. These 3 peptides were administered s.c. 3 times daily for 4 days at the following concentrations: 0.036, 0.36, 3.6 and 7.2 nmol/kg of body weight. Bombesin and GRP induced pancreatic growth in a dose-dependent manner from 3.6 nmol/kg. This growth was characterized by an increase in pancreatic weight, its protein and RNA contents but not in DNA content suggesting cellular hypertrophy. Caerulein exerted a biphasic effect on pancreatic growth, inducing cellular hypertrophy at low doses since 0.36 nmol/kg and atrophy with the highest dose (7.2 nmol/kg). Bombesin and caerulein (until 3.6 nmol/kg) increased the pancreatic content in chymotrypsin more than in amylase. The 7.2 nmol/kg caerulein treatment depressed all enzyme activities while the same dose of GRP increased pancreatic lipase content. It is concluded that (1) bombesin and GRP are equipotent trophic factors for the pancreas; (2) caerulein is the most potent factor and exerts a biphasic effect on pancreatic growth; (3) pancreatic growth and synthesis and/or secretion of enzymes are not regulated through the same mechanism.