Abstract Amylin, a 37-amino-acid peptide co-secreted with insulin from the beta-cells of the pancreatic islets, has previously been demonstrated to inhibit bone resorption in vitro. However, its effects on bone formation and bone mass have not been assessed. We report that periphysiological concentrations of amylin stimulate proliferation of fetal rat osteoblasts in vitro. When amylin is injected daily for 5 days over the calvariae of adult mice in vivo, there are substantial increases in histomorphometric indices of bone formation, a reduction in bone resorption, and a significant increase in mineralized bone area. Equimolar doses of calcitonin in this in vivo model produced an inhibition of bone resorption but no significant effect on bone area. These findings support a role for amylin as a physiological regulator of bone and suggest that it should also be evaluated as a potential treatment for osteoporosis.