Therapeutic balloon coronary angioplasty provides a useful model for studying the effects of epicardial coronary artery occlusion in conscious humans. In addition, it is a potent model in which the effectiveness of interventions designed to ameliorate ischemia can be evaluated. Whereas intravenous beta-adrenergic blocking drugs and nitrates appear to have a limited protective effect, the regional (i.e., intracoronary) use of beta-adrenergic blocking drugs and calcium antagonists seem more potent. Currently, coronary venous retroperfusion with arterial blood does not appear practical, and the intraaortic balloon is a useful adjunctive measure in relatively few patients undergoing percutaneous transluminal coronary angioplasty. In contrast, the direct anterograde delivery of oxygen-rich blood or fluorocarbons holds promise as a reliable means of providing local myocardial protection. If ischemia could be markedly reduced, percutaneous transluminal coronary angioplasty might be applied safely in more high-risk clinical settings. In addition, if prolonged balloon inflation could be performed, there might be an increase in primary success rate and possibly a reduction in restenosis rate.