Exposure of the early gestation ovine fetus to exogenous glucocorticoids induces organ-specific alterations in postnatal cardiovascular physiology. To determine if early gestation corticosteroid exposure alters coronary reactivity prior to the development of systemic hypertension, dexamethasone (0.28 mg/kg/day) was administered to pregnant ewes by intravenous infusion over 48 hours beginning at 27 days gestation (term 145 days). Vascular responsiveness was assessed in endothelium-intact coronary arteries isolated from one week-old steroid-exposed and age-matched control lambs (N = 6). Calcium imaging was performed in fura 2-loaded primary cultures of vascular smooth muscle cells (VSMC) from the harvested coronary arteries. Early gestation steroid exposure did not significantly alter mean arterial blood pressure or coronary reactivity to KCl, thromboxane A₂ mimetic U46619, or angiotensin II. Steroid exposure significantly increased coronary artery vasoconstriction to acetylcholine and endothelin-1. Vasodilatation to adenosine, but not nitroprusside or forskolin, was significantly attenuated following early gestation steroid exposure. Endothelin-1 or U46619 stimulation resulted in a comparable increase in intracellular calcium concentration ([Ca²⁺]_i) in coronary VSMC isolated from either dexamethasone-treated or control animals. However, the angiotensin II- or KCl-mediated increase in [Ca²⁺]_i in control VSMC was significantly attenuated in VSMC harvested from dexamethasone-treated lambs. Coronary expression of Ca_V1.2 protein was not significantly altered by steroid exposure, while endothelial eNOS expression was attenuated. These findings demonstrate that early gestation glucocorticoid exposure elicits primary alterations in coronary responsiveness prior to the development of systemic hypertension. Glucocorticoid-induced alterations in coronary physiology may provide a mechanistic link between an adverse intrauterine environment and later cardiovascular disease.