Recurrent pancreatitis is more prevalent in the 4% of people with pancreas divisum (nonfused dorsal and ventral ducts), and it has been proposed that the pancreatitis is caused by stenosis at the orifice of the dorsal duct. We have treated 40 patients with pancreas divisum and proven or probable pancreatitis. The diagnoses were made by endoscopic pancreatography showing a foreshortened (less than 6 cm) ventral duct (Wirsung) and confirmed by postoperative pancreatograms showing the separate main duct (Santorini) emptying via the accessory papilla. Of these, 32 patients (25 men, 7 women, median age 30) had recurrent acute pancreatitis (22) or persistent pain (10) without chronic inflammation or fibrosis. Twenty-nine have been treated by transduodenal sphincteroplasty of the accessory papilla; 22 were stenotic (0.75 mm or less) and 7 nonstenotic. Among 25 patients observed for longer than 6 months after surgery, the relief of pain and pancreatitis has been good in 17, fair in 1, and poor in 7. There was no difference between accessory papillotomy alone (10-0-3) v papillotomies of both accessory and major papillae (7-1-4). Patients with stenosis (16-1-1) fared better (p less than 0.001) than those without stenosis (1-0-6). Those presenting with discrete attacks (12-1-2) also fared better (p less than 0.05) than those presenting with chronic pain (5-0-5). The other eight patients (two women, six men, median age 28) had chronic pancreatitis proven by pancreatography and surgical biopsy. In this group, treatment by sphincteroplasty of the accessory papilla failed, and seven patients eventually required a pancreaticojejunostomy (3), distal pancreatectomy (2), or total pancreatectomy (2). In pancreas divisum, pancreatitis is caused by stenosis at the accessory papilla of Santorini. There may be progression from recurrent acute pancreatitis to irreversible fibrosis in some cases. Sphincteroplasty is effective for recurrent acute pancreatitis, but ductal drainage or resection becomes necessary once chronic pancreatitis is established. A preoperative test for stenosis of the accessory papilla is needed to identify patients whose symptoms are genuinely caused by their pancreas divisum.