Transmyocardial laser revascularization (TMR) using a carbon dioxide (CO(2)) laser has been shown to relieve angina, increase vascular density, and improve myocardial contraction. A study of 28 patients receiving TMR was conducted to monitor vascular endothelial growth factor (VEGF) levels with the goal of clarifying the relationship between TMR, the amelioration of angina, and vascular density. Serum VEGF levels were measured during four periods (preoperative, postoperative, convalescence, and late) in these 28 patients who received sole therapy TMR for un-revascularizable ischemic angina and the levels were compared with the control group consisting of 10 nonischemic thoracotomy patients. Twelve of the 28 patients had previous coronary artery bypass graft(s); 10 had unstable angina, and 1 had an ejection fraction less than 30%. Overall, angina class was reduced from 3.8 +/- 0.9 to 1.0 +/- 0.9 (P < 0.01) at the 1-year follow-up. There were no perioperative mortalities; however, there was one late mortality. The results show that VEGF levels were higher in the convalescence and late periods. Specifically in the late period, VEGF levels in TMR therapy patients surpassed those of the control group and normalized VEGF levels were three times higher in the late period than preoperatively. The sustained VEGF secretion observed in this study may help to explain why CO(2) TMR therapy causes locally increased vascular density and angina relief.