Progressive physiological and mechanical changes in the medial collateral ligament of the adult rabbit were investigated for as long as 48 weeks after disruption of the anterior cruciate ligament. Eighty-one New Zealand White rabbits were separated into experimental, sham-operated control, and normal control groups. The experimental group underwent unilateral transection of the right anterior cruciate ligament, sham-operated animals served as controls for comparison, and normal animals were evaluated as age-matched, undisturbed (no surgery) controls. Blood flow to the medial collateral ligament (as a physiological measure) and mechanical function (structural and material properties) were assessed at 6, 14, and 48 weeks. The results indicated that loss of the anterior cruciate ligament leads to early mechanical deterioration of the medial collateral ligament with a corresponding loss of physiological homeostasis. Six to 14 weeks after the transection, values for cross-sectional area of the medial collateral ligaments rapidly increased to 1.5 times control values. The ligament became twice as large as the control ligament by 48 weeks. Concomitantly, medial collateral ligament stress at failure of the medial collateral ligament complex decreased rapidly 6-14 weeks after the transection and eventually fell to one-half that of controls by 48 weeks. In terms of low-load behaviour, laxity and load relaxation were significantly greater than that of controls 6 weeks after transection and were further increased by 14 weeks. By 48 weeks, laxity values had recovered somewhat and load-relaxation measures had recovered to near control values. At both 6 and 14 weeks, a statistically significant elevation in blood flow was demonstrated compared with controls. By 48 weeks, however, blood flow was no different from that of the sham-operated control. Thus, early after transection of the anterior cruciate ligament, both low-load and high-load mechanical properties of the medial collateral ligament deteriorated and the rate of blood flow was temporarily elevated. By 48 weeks, blood flow declined to near control values, with a corresponding recovery in viscoelastic behaviour. These findings suggest that, after transection of the anterior cruciate ligament, viscoelastic behaviour of the medial collateral ligament may be related to changes in blood flow and that restoration of normal flow patterns and vascular responses may be linked to the recovery of some low-load mechanical properties in the anterior cruciate ligament-deficient medial collateral ligament.