The efficacy of 1-vessel percutaneous transluminal coronary angioplasty (PTCA) directed at the presumed angina-producing stenosis, or "culprit lesion," in the treatment of unstable angina pectoris and multivessel coronary artery disease (CAD) was assessed in 27 patients with unstable angina refractory to optimal medical therapy. Eighteen patients had 2-vessel and 9 had 3-vessel CAD. The culprit lesion was identified in all patients by analysis of the qualitative appearance of the coronary lesions and detection of angiographic evidence of plaque fissuring or coronary thrombosis. Intracoronary filling defects were evident in 26% and eccentric stenoses with irregular edges were noted in 41% of patients. Subtotal obstructions were seen in 33%. Confirmation of the identity of the culprit lesion was also available in 78% of patients by analysis of the pattern and distribution of spontaneous electrocardiographic changes. The PTCA primary success rate was 89%, with no procedure-related complications. All patients in whom PTCA was successful had immediate resolution of their unstable angina. Follow-up of the successfully treated patients after a mean of 16 months (range 12 to 20) showed maintenance of long-term clinical improvement, with only 17% of patients having recurrent angina. These data suggest that 1-vessel PTCA of the culprit lesion may serve as a feasible therapeutic option in the treatment of selected patients with multivessel CAD and unstable angina.