The ligaments of weight-bearing joints are known to become mechanically inferior during pregnancy, and it has been postulated that this may be due to changes in tissue perfusion. Calcitonin gene-related peptide (CGRP) and epinephrine exert a tonic influence on the vasculature of the medial collateral ligament (MCL), and the present study examined whether these vasoactive influences were altered by pregnancy. Ligament perfusion experiments were performed on primigravid New Zealand White rabbits with the use of laser Doppler perfusion imaging. In pregnant animals (day 29), MCL basal perfusion fell significantly compared with control; however, values returned to normal 5 days postpartum. In normal joints, topical application of CGRP resulted in a dose-dependent increase in MCL perfusion, whereas epinephrine administration caused a dose-dependent fall in blood flow. During pregnancy, the vasodilator effect of CGRP was completely abolished, whereas adrenergic vasoconstriction was greater than normal. Both responses returned postpartum. Pregnancy in the rabbit produces hypoemia in the MCL, and this phenomenon may be effected by a tempering of CGRP dilator responses and an augmentation of alpha-adrenoceptor-mediated vasoconstriction.