Chronic hypoxia (CH) causes pulmonary vasoconstriction because of increased pulmonary arterial smooth muscle cell (PASMC) contraction and proliferation. We previously demonstrated that intracellular Ca²⁺ concentration ([Ca²⁺]_i) was elevated in PASMCs from chronically hypoxic rats because of Ca²⁺ influx through pathways other than L-type Ca²⁺ channels and that development of hypoxic pulmonary hypertension required full expression of the transcription factor hypoxia inducible factor 1 (HIF-1). In this study, we examined the effect of CH on the activity and expression of store-operated Ca²⁺ channels (SOCCs) and the regulation of these channels by HIF-1. Capacitative Ca²⁺ entry (CCE) was enhanced in PASMCs from intrapulmonary arteries of rats exposed to CH (10% O₂; 21 days), and exposure to Ca²⁺-free extracellular solution or SOCC antagonists (SKF96365 or NiCl₂) decreased resting [Ca²⁺]_i in these cells. Expression of TRPC1 and TRPC6, but not TRPC4, mRNA and protein was increased in PASMCs from rats and wild-type mice exposed to CH, in PASMCs from normoxic animals cultured under hypoxic conditions (4% O₂; 60 hours), and in PASMCs in which HIF-1 was overexpressed under nonhypoxic conditions. Hypoxia-induced increases in basal [Ca²⁺]_i and TRPC expression were absent in mice partially deficient for HIF-1. These results suggest that increased TRPC expression, leading to enhanced CCE through SOCCs, may contribute to hypoxic pulmonary hypertension by facilitating Ca²⁺ influx and increasing basal [Ca²⁺]_i in PASMCs and that this response is mediated by HIF-1.