The current study examines the effects of alpha-difluoromethylornithine (DFMO), an irreversible ornithine decarboxylase inhibitor, on pancreatic growth and development of rat neonates. Newborn rats were given daily subcutaneous injections of 300 or 500 mg kg-1 DFMO and killed after 7, 14, 21, and 28 days of treatment. Pancreatic weights and DNA, RNA, protein, amylase and chymotrypsin total contents (per pancreas) and concentrations were evaluated at the end of each period. Inhibition of body weight gain (30%) was maximal after 14 days of the 500 mg DFMO treatment. Pancreatic weight increase of 20% was significant after 7 days of the 300 mg DFMO treatment while deficits of 15, 20, and 14% were significant after 21 days of 300 mg DFMO and 14 and 21 days of 500 mg DFMO. Total DNA was already subnormal after one week of 500 mg DFMO with a maximal reduction of 30% after 28 days while a significant decrease of 15% was observed only after 3 weeks of 300 mg DFMO. Pancreatic hypertrophy was observed after 7 and 28 days of the 500 mg and after 14 days of the 300 mg DFMO treatment. Chymotrypsin total contents and concentrations were always preferentially affected over those of amylase. These data support the view that ornithine decarboxylase (ODC) and polyamines play an important role in cell replication and growth of the pancreatic tissue during the neonatal period.