The objective of this study was to assess the potential of phentolamine as a treatment of postmenopausal women with female arousal disorder (FSAD). Vaginal photoplethismography and a subjective questionnaire were used. Forty one women were enrolled and four treatments were tested: vaginal solutions 5 mg and 40 mg and an oral tablet each of 40 mg of phentolamine and placebo. Physiological readings were significantly different from placebo in the women using hormone replacement therapy (HRT) with 40 mg of phentolamine in vaginal solution (p = 0.0186). Subjective reports also were significantly different from placebo with the vaginal solution 40 mg and the oral tablet of 40 mg of phentolamine among hormone replacement users. No significant differences were found among women not receiving HRT. Results indicate that phentolamine may show promise as treatment for FSAD in estrogenized postmenopausal women.