Previous studies have demonstrated the development of vasoconstriction immediately after percutaneous coronary angioplasty (PTCA), distal to the dilated stenosis, presumably resulting from endothelial injury. We have investigated the role of 5-HT2 receptors in mediating vasomotor changes in proximal and distal coronary segments and coronary stenoses, immediately after successful PTCA in patients with chronic stable angina. We compared the effects of the intracoronary infusion of 1 mg ketanserin (5-HT2 receptor antagonist) on proximal and distal coronary arterial segments immediately after PTCA in both vessels subjected to PTCA and control vessels. Coronary diameters, before and after angioplasty and after ketanserin administration, of proximal and distal segments and coronary stenoses were measured by computerized quantitative coronary angiography (CAAS system) in 12 patients (10 male, two female; mean age 54 +/- 6 years) with stable angina subjected to PTCA. After coronary angioplasty, vasoconstriction was observed in the segment distal to the dilated stenosis but not in the distal segments of control vessels (-0.12 +/- 0.04 and -0.02 +/- 0.02 mm respectively; P < 0.05). After ketanserin infusion significant dilatation was found in the distal segments of both PTCA vessels and control vessels, but the dilatation was greater in the PTCA vessels (P < 0.05). No significant changes were found in the proximal segments of either PTCA or control vessels, or at the PTCA site. In conclusion, the vasoconstriction distal to the site of PTCA is mediated, at least in part, via 5-HT2 receptors.