An animal model was used to examine the use of noninvasive transmission ultrasound to measure changes in bone mass which occur following disuse. Unilateral achilles tenectomy was performed on the left leg of eight adult sheep. Following a 12-week period of nonweight bearing, presacrifice transmission ultrasound measurements were taken across the calcanei of the intact and the experimental limbs and compared with those values taken postoperatively. Following specimen harvest, cross-sectional areas of the bones were quantified by microradiography and stereology, and compared with the in vivo ultrasound measurements. There was an average of 8.6% less total bone area, and 18.0% less trabecular volume fraction in the experimental nonweight-bearing limbs as compared with control intact calcanei. The difference in bone mass was associated with a 9.0% decrease in the velocity of sound from the postoperative to the presacrifice ultrasound measurements taken from the experimental calcanei, and a 2.3% increase in the control calcanei. The velocity of sound was found by the Student's t test to be a highly reliable discriminator between the experimental and control limbs.