Little is known about the contribution of innervation to ligament healing after traumatic disruption, although there is good evidence of an important role for the peripheral nervous system in the healing of fractures and skin injuries. Tissues such as ligament, with a low resting blood supply, are dependent on substantial increases in blood flow and vascular volume during the initial stages of repair. We hypothesized that this initial healing response would be strongly promoted by neurogenic inflammation. Since the saphenous nerve (a major sensory branch of the femoral nerve) supplies the medial half of the knee joint, we elected to use femoral nerve transection as a model to determine the role of sensory and autonomic innervation in the initial outcome of repair of the injured medial collateral ligament. Twelve adult, female NZW rabbits underwent right medial collateral ligament transection. Of these, six rabbits underwent right femoral nerve transection to disrupt the somatic sensory and autonomic nerve supply to the knee joint and six were kept neurologically intact (controls). At six weeks post-injury, the animals were assessed by laser Doppler perfusion imaging (LDI) to determine the local blood flow, at both the injury site and at the uninjured contralateral ligament. The animals were then killed, the knee joints were removed and the biomechanical characteristics of the healing bone-median collateral ligament (MCL)-bone complexes assessed. In a separate cohort of 16 rabbits, vascular volumes of the injured ligaments were measured by infusion of a carmine red/gelatin solution. At six weeks post-injury, in vivo measurement of perfusion with LDI revealed that normally innervated ligaments had an almost three-fold higher average blood flow. Carmine red/gelatin infusion revealed a 50% higher density of blood vessels as compared to denervated ligaments. The force required for ultimate failure was found to be 50% higher in normally innnervated MCL's as compared to denervated MCL's: 153.14 +/- 20.71 N versus 101.29 +/- 17.88 N (p < 0.05). Static creep was increased by 66% in denervated MCL's: 2.83 +/- 0.45% versus 1.70 +/- 0.12% (p < 0.05). Total creep was increased by 45% in denervated MCL's: 5.29 +/- 0.62% compared to 3.64 +/- 0.31% in innervated MCL's (p < 0.05). We conclude that intact innervation makes a critical contribution to the early healing responses of the MCL of adult rabbits.