Pulmonary arterial hypertension (PAH) is characterized by an elevated, sustained increase in pulmonary artery pressure and eventual right heart failure. Caveolins (cavs) are the primary structural proteins of caveolae that function as chaperones and scaffolding proteins to caveolae for temporal and spatial regulation of signal transduction, and evidence suggests that caveolin-1 (cav-1) gene and protein expression is altered in severe pulmonary hypertension. BKCa channels are important regulators of pulmonary arterial smooth muscle cell (PASMC) function, and evidence suggests a functional interaction between cav-1 and BKCa channels. Therefore, the present study determined the effect of cav-1 signaling on BKCa channel activity in PASMC of the hypertensive Fawn-Hooded rat (FHR), and in PASMC of the normotensive Sprague-Dawley rat (SDR). Cav-1 gene and protein expression was decreased in PASMC from FHR and functionally, caveolin-1 disruption decreased pulmonary vasodilation by BKCa channel activation in pulmonary arteries from SDR to a greater extent than in vessels from FHR. Further, confirmatory data indicated that cav-1 increased BKCa channel activity in HEK293 cells. These results suggest that cav-1 positively regulates BKCa channel activity in the pulmonary vasculature, which may be germane towards further understanding signaling mechanisms of pulmonary hypertension.