We examined the spectrum of intermediate cell types in the regenerating pancreas as duct epithelial cells progressed through their differentiation pathway to become mature endocrine cells. The model used was transgenic mice in which the pancreatic islets continue to grow during adulthood, unlike normal mice whose islet cell formation ceases early in life. Because the intermediate cells migrated into islet-like clusters at specific locations, we propose a specific pathway for islet development. Endocrine cells are derived from duct cells co-expressing a duct cell antigen, carbonic anhydrase II (CA II) and an exocrine enzyme, amylase. The CA II/amylase cells become amylase/endocrine intermediate cells as they exited from their lumenal location. The abluminal amylase/endocrine cells continue to differentiate to multihormone-bearing young endocrine cells, which migrated to form clusters with other differentiating endocrine cells.