Purpose: This study assessed whether intracoronary brachytherapy after percutaneous transluminal coronary angioplasty (PTCA) affects the peripheral venous plasma endothelin-1 (ET-1) levels and whether changes in ET-1 levels are associated with 6-month restenosis. Methods: Thirteen and 12 study patients who received post-PTCA 20-and 14-Gray (Gy) intracoronary β-irradiation, respectively, were enrolled. Six control patients received 5 minutes of post-PTCA inflation with a perfusion balloon catheter. Blood samples for plasma ET-1 levels measurements were collected immediately before, at I hour and 24 hours after PTCA procedures from the antecubital vein. Results: Compared to pre-PTCA, ET-1 levels of the 14-Gy and 20-Gy irradiation groups were significantly higher at 1-hour post-PTCA and returned to baseline after 24 hours (8.23±3.09 vs. 10.21±4.84 vs. 7.91±3.97 pg/ml; p=0.04 and 8.53±3.25 vs. 16.08±10.45 vs. 9.75±3.51 pg/ml; p=0.004. respectively). There were no significant changes in ET-1 levels measured in the control group (9.92±4.42 vs. 7.51±2.08 vs. 7.79±4.60 pg/ml; p=0.144). The transient increase of ET-1 levels was strongly associated with higher inflation time (multiple linear regression analysis: p=0.002). The 6-month angiographic restenosis rates of the control, 14-Gy irradiation and 20-Gy irradiation groups respectively, were 50%, 33% and 23% (p=0.50) and were not associated with transient increases of ET-1 levels. Conclusion: A transient increase in the peripheral plasma ET-1 levels was caused by lengthy perfusion balloon inflation after PTCA during intracoronary irradiation with Re-188, and this increase was not associated with an increased 6-month restenosis rate.