Recent reports have shown that /3-adrenergic blockade may exacerbate variant angina. On theoretical grounds, ca-adrenergic blockade may be beneficial in these patients. To test this hypothesis, we assessed the efficacy of prazosin, an ca-adrenergic blocking agent, in six men, mean age 49 years, with variant angina. Prazosin, 14.0 ± 2.4 mg/day (mean SD) in three equal doses, was compared with placebo in a double-blind, randomized, double-crossover trial lasting 41/2 months: 2 weeks of open-label prazosin followed by four 1-month periods of blinded alternating therapy. No other vasoactive medications were administered during the study. Prazosin reduced sitting systolic arterial pressure from 145 18 to 127 16 mm Hg (p = 0.02), but exerted no effect on diastolic arterial pressure or heart rate. Prazosin did not change the weekly number of episodes of chest pain (2.5 2.3 with placebo vs 3.1 3.0 with prazosin, NS), nitroglycerin tablets used (3.9 3.7 with placebo vs 4.6 4.2 with prazosin, NS), or transient ST-segment deviations (by calibrated two-channel Holter monitoring for 24 hours/week throughout the study) (6.5 ± 10.1 with placebo vs 11.8 17.4 with prazosin, NS). During prazosin therapy, three patients had orthostatic dizziness and one patient had headache. Thus, in a long-term, randomized, double-blind trial, prazosin exerted no obvious beneficial effect in patients with variant angina.