In order to investigate whether smooth muscle intracellular calcium levels ([Ca2+]i) are related to hypertension and drug-induced changes in blood pressure, we studied basal perfusion resistance and basal [Ca2+]i and increases in perfusion pressure and [Ca2+]i using the fluorescent dye, fura-2 (dual wavelength excitation) in perfused tail artery. These were removed from 6 month old SHR previously treated (CAP + HCZ) for 10 weeks with captopril plus hydrochlorothiazide (44 and 22 mg/kg/day po, respectively). Separate groups received captopril (CAP) or hydrochlorothiazie (HCZ) alone, at similar doses, or no treatment (SHR). A fifth group of WKY normotensive rats did not receive any drug. Following determination of systolic arterial pressure (SAP) in awake rats, tail artery segments were removed and perfused at a constant flow rate with physiological salt solution plus fura-2/AM. Basal resistance and [Ca2+]i were determined. Then a dose-response curve for calcium chloride in the presence of a depolarizing concentration of potassium chloride was constructed. SAP was lowered in groups CAP + HCZ or CAP, but not in the group HCZ. Basal [Ca2+]i were similar in treated and untreated SHR and in WKY. Basal resistance to flow was lower in groups CAP + HCZ or CAP, and in WKY, than in untreated SHR. In depolarized arterial segments, vasconstrictor responses to perfusion with calcium chloride were lower in groups CAP + HCZ or CAP, and in WKY. Increases in [Ca2+]i were diminished in WKY rats. SAP measured in awake SHR and WKY was significantly correlated to basal and stimulated intracellular calcium-vasoreactivity coupling measured in vitro.