On the basis of earlier findings of increased serum beta 2-microglobulin concentration in women with postmenopausal osteoporosis, we decided to study serum beta 2-microglobulin concentration in other bone diseases. In 28 patients with untreated Paget's bone disease, serum beta 2-microglobulin concentration was normal (1.49 +/- 0.41 mg/liter versus 1.36 +/- 0.21 mg/liter in 42 control subjects, P = ns), a finding that contradicts reports in the literature. We found that serum beta 2-microglobulin concentration was related negatively and significantly (r2 = -0.154, P = 0.0354) with serum total alkaline phosphatase concentration, but not with serum tartrate-resistant acid phosphatase concentration (p = ns). Urinary elimination of beta 2-microglobulin was lower in the patients with Paget's disease than in the controls (34 +/- 28 versus 120 +/- 21 mg/liter, P < 0.001). These findings suggest that beta 2-microglobulin behaves similarly to osteocalcin (BGP) in Paget's bone disease and that its concentration remains within normal levels perhaps because of the rate of reuptake of beta 2-microglobulin in bone neoformation.