Recent studies indicate that serum levels of osteocalcin, a 49-aminoacid bone matrix protein, are a biochemical marker of bone formation. In order to study bone metabolism in diabetes mellitus, in 28 patients with Type 1 (insulin-dependent) diabetes mellitus, in 38 patients with Type 2 (non-insulin-dependent) diabetes mellitus and two control groups, matched for Type 1 and Type 2 diabetic patients, respectively, serum levels of osteocalcin, parathyroid hormone and 25 hydroxy vitamin D were measured by radioimmunoassay. Whereas in Type 1 diabetic patients and control subjects serum levels of osteocalcin and 25 hydroxy vitamin D were not statistically different, serum osteocalcin and 25 hydroxy vitamin D levels were significantly decreased in Type 2 diabetic patients when compared with corresponding control subjects (p less than 0.03 and p less than 0.001, respectively). Independent of the type of diabetes, serum parathyroid hormone levels were comparable in diabetic patients and matched control subjects. Serum osteocalcin levels were significantly lower in Type 1 diabetic patients with retinopathy and/or proteinuria than in Type 1 diabetic patients without microangiopathy (p less than 0.05). Whereas serum parathyroid hormone levels in Type 2 diabetic patients with retinopathy and/or proteinuria were significantly increased (p less than 0.02), 25 hydroxy vitamin D levels were decreased (p less than 0.02) when compared with Type 2 diabetic patients without microangiopathy. Our data give evidence of a vitamin D deficiency and a decreased bone formation in patients with Type 2 diabetes mellitus. In Type 1 diabetes mellitus bone formation as reflected by serum osteocalcin levels is influenced by the presence or absence of microangiopathic complications.