While abnormal hemodynamic forces alter fetal myocardial growth, little is known about whether such insults dysregulate fetal cardiac valve development. We hypothesized that chronically elevated systolic load would detrimentally alter fetal valve growth. Sixteen chronically instrumented fetal sheep received either a continuous infusion of adult sheep plasma to increase fetal blood pressure (n=8), or a Lactated Ringers infusion as a volume control (n=8) beginning on day 126±4 of gestation. After 8 days, mean arterial pressure was higher in the plasma infusion group (63.0 mm Hg vs. 41.8 mm Hg, P < 0.01). Mitral annular septal-lateral diameter (11.9 mm vs. 9.1 mm, P < 0.05), anterior leaflet length (7.7mm vs. 6.4 mm, P < 0.05), and posterior leaflet length (4.0 mm vs. 3.0 mm, P < 0.05) were greater in the elevated load group. mRNA levels of Notch-1, TGF-β2, Wnt-2b, BMP-1, and versican were suppressed in aortic and mitral valve leaflets; elastin and alpha-1 type I collagen mRNA levels were suppressed in the aortic valves only. We conclude that sustained elevated pressure load on the fetal heart valve leads to anatomic remodeling and, surprisingly, suppression of signaling and extracellular matrix genes that are important to valve development. These novel findings have important implications on the developmental origins of valve disease and may have long term consequences on valve function and durability.