Several recent studies have suggested that the adult bone marrow harbors cells that can differentiate into tissues from all three germ layers. Other reports have contradicted these findings or attributed them to cell fusion. In this study, we investigated whether bone marrow−derived cells contribute to the renewal of adult pancreatic endocrine cells, in particular insulin-producing β-cells, in vivo. To address this issue, we studied mice transplanted with green fluorescent protein (GFP)−positive, sex-mismatched bone marrow. We also extended our studies to pancreatic injury models (partial pancreatectomy and streptozotocin administration). All animals showed stable full donor chimerism in the peripheral blood and microscopic analysis at 4–6 weeks and 3 months after transplantation, indicating that the GFP⁺ and Y chromosome−positive donor bone marrow contributed substantially to blood, lymphatic, and interstitial cells in the pancreas. However, after examining >100,000 β-cells, we found only 2 β-cells positive for GFP, both of which were in control animals without pancreatic injury. Thus our study results did not support the concept that bone marrow contributes significantly to adult pancreatic β-cell renewal.