Diabetes and osteoporosis are linked. The question remains, however, as to whether insulin has any direct effect on bone formation. To test this hypothesis we have measured, as a marker of osteoblast activity, alkaline phosphatase (ALP) released by rat limb intact bones incubated in the presence and in the absence of physiological concentration of insulin. The results indicate that insulin significantly (p less than 0.012) increases ALP by a mean value of 48% (from 5.4% to 215%) over matched controls. We conclude that insulin has a direct stimulatory effect on osteoblast activity, and that in the absence of this effect, as in diabetes, bone loss might occur.