Drugs and diseases have differential effects on functional and structural components of large-conduit arteries and smaller vessels. The objective of this study was to demonstrate functional and structural effects of doxazosin (DOX) on large-vessel and small-vessel arterial elasticity in hypertension (HTN). This was an open-label, single-blind, active-therapy study. Patients with stage 1 to 2 HTN were administered DOX 2 mg/day for 3 months and 4 mg/day for 1 month, if indicated, followed by 2-week washout period. Arterial elasticity was measured noninvasively at baseline, at 3 months and 4 months of treatment, and 2 weeks following DOX withdrawal. Although the observed effects were not statistically significant, large-vessel elasticity (C1) increased in a dose-related manner and returned to baseline 2 weeks after drug withdrawal. There was a trend toward an increase in small-vessel elasticity in a dose-related manner. However, 2 weeks after drug withdrawal, C2 (distal elasticity) had not returned to baseline and was statistically significantly different from baseline (p = 0.032). It was concluded that large-artery compliance increased in a dose-related manner. Almost all benefit was lost within 2 weeks of discontinuation, suggesting the DOX effect was functional. Small-artery compliance improved in a dose-related manner but only partially returned to baseline after DOX withdrawal, suggesting changes in artery structure by DOX. ©2002 the American College of Clinical Pharmacology.