The present study was to investigate whether combined imaging of 81Rb and 81mKr distributions after i.v. injection of 81Rb at rest might improve the differentiation between ischemic and irreversibly damaged myocardium as compared to 201Tl scintigraphy at rest. In 21 patients who had undergone diagnostic cardiac catheterization for evaluation of chest pain, 148 MBq ultrapure 81Rb were injected i.v. at rest immediately following 201Tl scintigraphy at rest. Of 14 patients with earlier myocardial infarction, 10 patients revealed decreased regional tracer uptake of 81Rb and/or 81mKr, compared to 12 patients with regional 201Tl uptake abnormalities. In 3 patients with unstable angina pectoris, however, an evident mismatch between either the regional 201Tl or 81Rb distributions and the distribution of 81mKr was observed: in contrast to the reduced uptake of 201Tl and/or 81Rb, 81mKr activity was increased in 3 myocardial segments with normal left ventricular performance but supplied by coronary arteries with high-grade stenoses. In patients with contraindications to exercise tests (e.g. unstable angina) 81Rb/81mKr rest scintigraphy may therefore assist the differentiation between malperfused but potentially viable and irreversibly damaged myocardium.