The aim of this study was to evaluate the effects of the transdermal application of nitroglycerin (NGT) on exercise tolerated and regional myocardial perfusion, as evaluated by 201 thallium stress scintigraphy, in patients with stable effort angina. We studied 20 patients, 15 men and 5 women, aged between 43 and 68 years, with average age of 55 +/- 8 years, suffering from effort angina, whose angina threshold was stable in 3 stress testing performed in the week before the study started. The patients, after a pharmacological washout of 1 week, underwent 2 exercise testing 20 hours after the application of a patch containing placebo or 10 mg NGT, with an interval of 7 days. 60-90 s before stress testing was interrupted, 2 mCi of thallium 201 were injected in an antecubital vein of the arm. The scintigraphic images were obtained soon in the 0, 45 and 90 degree views and after 4 hours reperfusion. Under placebo patch all patients interrupted ergometer test for angina, while under the patch containing active NGT angina was present in 11/20 patients and 9 patients stopped the test because of muscular exhaustion. NGT induced an increase of the ergometer test duration (+26%); this difference was statistically significant. The ST segment downsloping decreased significantly both at maximal common work and at exercise peak after NGT application in comparison with placebo. The perfusional defects observed on the scintigraphic images obtained soon after the exercise (and reversible after 4 hours of reperfusion) on placebo patch, diminished significantly after NGT and the captation index lung/heart decreased also significantly (from 49 to 41%), showing so an improvement of cardiac performance. In conclusion the transdermal application of NGT, in patients with effort angina, demonstrated to have antianginal and antiischemic effect, reducing the number of patients interrupting the stress testing for angina, increasing the exercise tolerated and diminishing the ST segment downsloping, objective demonstration of myocardial ischemia. This antianginal and antiischemic effect might follow to the reduction of the preload induced by nitrates, in part also the reduction of the afterload, factors determining a decrease of the wall tension and so of MVO2, but also to a redistribution of the subendocardial flow as demonstrated by 201-Tl scintigraphic images. These effects induce also a global improvement of the left ventricular function as demonstrated by the reduction of the lung/heart index of thallium captation.