The use of yohimbine to treat impotence has suggested that decreased male sexual desire may relate to decreased activity of central noradrenergic neurons. Previous trials of yohimbine to treat female sexual problems are not available. Yohimbine is an alpha 2-adrenergic antagonist that stimulates norepinephrine (NE) release. In the present study, plasma concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), the major central nervous system metabolite of NE, were measured in 9 women diagnosed with hypoactive sexual desire. Daily logs of mood and sexual activity, and trimonthly MHPG blood drawings, were obtained over an initial baseline menstrual cycle followed by two subsequent treatment cycles (yohimbine or placebo), in randomized order. Blood samples were obtained at 9:00 a.m. during (a) the early follicular phase of each cycle (24 hr after the onset of each cycle), (b) the ovulatory phase (i.e., within 1 day of an oral temperature rise), and (c) the midluteal phase (i.e., 20-25 days into each cycle). Comparisons were made with a group of 7 healthy female controls. Women with hypoactive sexual desire had slightly lower plasma MHPG values than controls at baseline, although there was only a trend toward significance during the early follicular phase (p = .09). Yohimbine (5.4 mg orally, 3 times daily, beginning at menses) caused a sustained rise in plasma MHPG of similar magnitude to that reported in men. However, in terms of improved sexual desire, yohimbine had no obvious therapeutic effect. Thus, plasma MHPG and the alpha 2-adrenergic response to yohimbine appeared within normal ranges in women with hypoactive sexual desire, with no therapeutic response to yohimbine.