Female sexual arousal disorder (FSAD) is a highly prevalent problem, although little is known about pathophysiology or treatment of the disorder. Given the potential role of vascular mechanisms, a small pilot study was conducted on the effects of oral phentolamine in menopausal women with FSAD. Six postmenopausal women with a lack of lubrication and with sexual arousal difficulties of at least 6 months duration participated in the study. All subjects received a single dose of oral phentolamine (40 mg) and placebo in a single-blind, dose-escalation design. Dependent variables for the study included vaginal pulse amplitude (VPA), as measured by vaginal photoplethysmography, self-report measures of sexual response, and patient- and physician-based assessments of adverse events. Results indicated a mild, positive effect of phentolamine across all measures of arousal, with significant changes (p < .05) in self-reported lubrication and pleasurable sensations in the vagina. The drug was well tolerated, overall, with few reports of adverse side effects. Further studies are needed to assess the potential value of phentolamine and other vasoactive agents in the treatment of female sexual dysfunction.