Nitroglycerin (Ntg) is known to increase blood flow to the hypoperfused myocardial area and thus to reduce regional ischaemia of the heart muscle in coronary artery disease (CAD). The aim of this study was to assess the effect of a therapeutic dose of Ntg on 99mTc-Tetrofosmin uptake defects occurring in patients (pts) with CAD in myocardial SPECT at rest. The study population comprised 34 pts with CAD. All subjects underwent myocardial perfusion SPECT at rest, using 2-day, protocol. On the first day 99mTc-Tetrofosmin was injected in baseline conditions and on the second day, after sublingual administration of 0.5 mg Ntg. The baseline examination revealed altogether 78 Tetrofosmin uptake defects in all 34 pts. The SPECT after Ntg showed improved tracer uptake in 33/78 perfusion defects in 18/34 pts, no change in 29/78 defects in 7/34 cases and more reduced tracer uptake in 16/78 defects in 9/34 pts. No explicit, significant relationship was found between 99mTc-Tetrofosmin uptake changes after Ntg on the one hand and the number of involved vessels, degree of coronary artery stenosis, history of myocardial infarction and LV global and regional function on the other. It is concluded that sublinqual administration of Ntg may result in improvement as well as in deterioration of regional perfusion defects, assessed with 99mTc-Tetrofosmin in CAD. The relationships between Ntg-augmented changes in uptake defects of this tracer on the one hand and conditions of the LV function and severity of heart muscle perfusion abnormalities on the other are unclear and should be verified on a larger study population.