The stretch-induced myogenic response (MR) of large-capacitance pulmonary arteries were studied in normal and pulmonary hypertensive fetuses as well as normal newborn and adult sheep. Pulmonary hypertension in the fetus was induced by ligation of the ductus arteriosus for 12 d. The MR was obtained by stretching the vessel segmentsin vitrofrom their resting diameter (no load) to the diameter at which the muscle fibers were at optimal length (Lo), and the response was measured as a percentage of force obtained after supramaximal electrical stimulation (Po). In five control and four pulmonary hypertensive fetuses, the MR was also obtained after a stretch of 140% of Lo. The pulmonary hypertensive fetal arteries had a lower stress (1.3 ± 0.4versus4.0 ± 0.5 mN/mm2;p< 0.001) and shortening capacity compared with the fetal control (5.1 ± 1.6versus9.9 ± 0.8% of Lo;p< 0.01). The MR was observed in 21% of the control and 30% of the experimental fetuses, and it was of greater magnitude in the latter (14.8 ± 1.9 of Poversus34.3 ± 2.5%, respectively;p< 0.01). When stretched to 140% of Lo, the MR was also greater in the experimental (514 ± 148% of Po) than the control fetuses (142 ± 68;p< 0.05). Postnatally, the MR was present in 67% of the newborn and 15% of the adult pulmonary artery segments, and the response was greatest in the newborn (23.1 ± 4.2% of Po) compared with the adult (2.3 ± 0.8;p< 0.01). These data indicate that the stretch-induced MR of large-capacitance pulmonary arteries of the sheep shows significant developmental differences postnatally and is greatly enhanced in the fetus after pulmonary hypertension. We speculate that large-capacitance arteries play a role in the control of pulmonary vascular resistance in pulmonary hypertension as a result of wall stiffness changes in response to intravascular pressure-induced MR.