To determine the effects of hydrocortisone and caerulein (separately and in combination) on the exocrine pancreas of suckling, recently weaned, growing, and adult rats, we administered hydrocortisone (0.5 mg/100 g body wt), caerulein (1 microgram/kg), and a combination of these two hormones for 3 days. The rats were killed, and the pancreas was weighed and analyzed for DNA, protein, amylase, and chymotrypsinogen. Caerulein alone was associated with significant decreases in amylase, chymotrypsinogen, and protein concentration in suckling rats; after weaning, it produced significant increases of these same parameters, representative of pancreatic hypertrophy. Hydrocortisone caused significant increases in DNA content and enzyme and protein concentrations in suckling rats; after weaning, the steroid significantly decreased DNA content in 26-day-old rats, but increases in enzyme and protein concentration were observed. Using an increase in DNA content as an index of hyperplasia and cellular mass and enzyme and protein concentrations as indices of hypertrophy, we conclude that over a 3-day period 1) caerulein produced pancreatic hypertrophy after weaning while potentiating the hyperplastic and hypertrophic action of hydrocortisone in suckling rats; and 2) hydrocortisone potentiated the hypertrophic effect of caerulein after weaning. The data suggest that these two hormones may regulate acinar cell proliferation and enzyme synthesis of the exocrine pancreas.