The relation between blood flow and bone mineral density (BMD) of periarticular bone was examined in an in vivo model of joint instability. Eighty mature New Zealand White rabbits were randomly assigned to experimental [anterior cruciate ligament transection (ACLX)], sham-operated control, or age-matched normal control groups. Experimental rabbits underwent unilateral transection of the right anterior cruciate ligament, and the nonoperated left [contralateral (Cntra)] limb was a within-animal control. BMD and blood flow to the periarticular bone in the femoral condyles were assessed in each group at 2, 4, 6, 14, and 48 wk postsurgery, using quantitative computed tomography scanning and entrapment of colored microspheres. BMD was significantly lower (5%) in the ACLX compared with Cntra limbs. Periarticular bone blood flow in the ACLX limbs was significantly greater than in the Cntra limb (29%) in the early stages (6 wk) after injury. Up to 48 wk post-ACLX, a significant correlation was found between increased blood flow and decreased BMD in the periarticular bone of the femoral condyles in the ACLX limbs. This correlation suggested that heightened blood flow may be linked to mechanisms of bone adaptation in joints after ligament injury.