Quantitative ultrasound (QUS) is currently being investigated as a possible alternative or adjunct to X-ray-based methods for assessing osteoporosis and fracture risk. It has been proposed that QUS may allow measurement of bone "quality," such as bone architecture or material properties. In this study, we used human cadaveric specimens to evaluate whether ultrasound velocity measurements performed in situ at the midtibia were correlated with the mechanical properties of tibial cortical bone. We obtained 26 human lower limbs (10 men and 16 women) with a mean (+/-SD) age of 81 +/- 12 and range of 53-98 years. The longitudinal ultrasound velocity of the cortical bone at the anteromedial midtibia (tUV, meters per second) was assessed in the intact legs (SoundScan 2000, Myriad Ultrasound, Rehovot, Israel). Then a cylinder of cortical bone was removed from the anterior tibia at the site of QUS scanning, scanned using peripheral quantitative computed tomography to determine bone density, and mechanically tested in tension to failure. We found that tUV of the intact legs correlated strongly with bone density of the cortical bone specimens (r2 = 0.74, p < 0.0001). Both bone density (r2 = 0.89, p < 0.0001) and tUV (r2 = 0.84, p < 0.0001) were very strongly correlated with the cortical bone elastic modulus. In addition, both tUV (r2 = 0.75) and bone density (r2 = 0.80) were highly correlated with the ultimate strength of the cortical bone specimens. In summary, tibial ultrasound velocity measured in situ correlated with the material properties of tibial cortical bone nearly as strongly as did bone density. (Bone 21:119-125; 1997).