Coronary vasoconstriction that occurs after percutaneous transluminal coronary angioplasty (PTCA) is abolished by intracoronary phentolamine. An impairment of coronary vasodilator reserve (CVR) has been observed < or = 7 days after successful PTCA. To ascertain whether pretreatment with the alpha1-adrenergic receptor blocker doxazosin could prevent the limitation of CVR after PTCA, we carried out a randomised, double-blind, controlled study on 26 patients with significant (> 75%) single vessel disease undergoing PTCA. Twelve patients received doxazosin 4 mg daily in addition to their standard treatment, while 14 patients received matching placebo, starting 11 days before PTCA. Myocardial blood flow (MBF) at baseline and after i.v. dipyridamole (0.56 mg/kg) was measured within 5 days after PTCA using positron emission tomography (PET) with oxygen-15-labelled water. Angioplasty was successful in all patients with a residual stenosis < or = 35%. At PET scanning, hemodynamic parameters were comparable in the two groups. In the territory subtended by the dilated artery, CVR was significantly higher in patients treated with doxazosin compared with those receiving placebo (2.78 +/- 0.1.21 vs. 1.95 +/- 0.68; p < 0.01). Conversely, CVR in the remote territories subtended by angiographically normal arteries was similar in the two groups (2.53 +/- 0.92 and 2.48 +/- 0.80, respectively; p = NS). Treatment with oral doxazosin in addition to standard antianginal therapy can prevent the impairment of CVR frequently observed despite successful PTCA.