Inhibition of voltage-gated, L-type Ca²⁺ (Ca_L) channels by clinical calcium channel blockers provides symptomatic improvement to some pediatric patients with pulmonary arterial hypertension (PAH). The present study investigated whether abnormalities of vascular Ca_L channels contribute to the pathogenesis of neonatal PAH using a newborn piglet model of hypoxia-induced PAH. Neonatal piglets exposed to chronic hypoxia (CH) developed PAH by 21 days, which was evident as a 2.1-fold increase in pulmonary vascular resistance in vivo compared to piglets raised in normoxia (N). Transpulmonary pressures (P_T) in the corresponding isolated perfused lungs were 20.5 ± 2.1 mm Hg (CH) and 11.6 ± 0.8 mm Hg (N). Nifedipine reduced the elevated P_T in isolated lungs of CH piglets by 6.4 ± 1.3 mm Hg, but only reduced P_T in lungs of N piglets by 1.9 ± 0.2 mm Hg. Small pulmonary arteries from CH piglets also demonstrated accentuated Ca²⁺-dependent contraction, and Ca²⁺ channel current was 3.94-fold higher in the resident vascular muscle cells. Finally, although the level of mRNA encoding the pore-forming _1C subunit of the Ca_L channel was similar between small pulmonary arteries from N and CH piglets, a profound and persistent upregulation of the vascular _1C protein was detected by 10 days in CH piglets at a time when pulmonary vascular resistance was only mildly elevated. Thus, chronic hypoxia in the neonate is associated with the anomalous upregulation of Ca_L channels in small pulmonary arteries in vivo, and the resulting abnormal Ca²⁺-dependent resistance may contribute to the pathogenesis of PAH.