Calcitonin gene-related peptide (CGRP) may play a role in regulation of pulmonary vascular tone in adults. We set out to establish whether or not CGRP has any effect on the fetal pulmonary circulation. Hemodynamic effects of exogenous CGRP were studied in seven near-term fetal sheep. Single CGRP injections into left pulmonary artery (LPA), compared with acetylcholine, and five repeated CGRP injections were studied. Single CGRP injections (1.36 ± 0.13 µg/kg) increased LPA blood flow (transit time ultrasound) significantly, from 26 ± 22 to 202 ± 86 ml/min (P < 0.05), and decreased pulmonary and aortic pressures, from 58 ± 5 to 48 ± 6 mmHg and from 56 ± 3 to 46 ± 5 mmHg, respectively (P < 0.05). LPA resistance decreased from 3.69 to 0.24 mmHg · min · ml¹ (P < 0.05). These changes were similar to those with acetylcholine. Five CGRP injections at 5-min intervals increased LPA flow significantly, in stepwise fashion, and LPA resistance decreased. Heart rate increased stepwise, without changes in pulmonary or carotid arterial pressures. Exogenous CGRP is a potent pulmonary vasodilator in fetal sheep and increases pulmonary flow. CGRP-induced increases in heart rate are not secondary to decreased systemic blood pressure but reflect a positive chronotropic effect. These findings suggest a role for endogenous CGRP in the remarkable decrease in pulmonary vascular resistance during the transition to extrauterine life.