Two hundred and thirty-one patients underwent dual-isotope myocardial imaging (rest thallium-201 followed by stress technetium-99m sestamibi). The feasibility of the procedure was excellent: camera scheduling flexibility was improved and the duration of the procedure was less than that of a classical stress-redistribution procedure. Interpretation of defects due to image attenuation was facilitated by the different attenuation properties of Tl-201 and Tc-99m-sestamibi in 11 of 19 patients. Tl-201 cross-over on Tc-99m was found to be 15% +/- 3% with doses of Tl-201 and Tc-99m-sestamibi of 3 and 10 mCi, respectively, and 7% +/- 2% with doses of 3 and 20 mCi. This protocol should preferentially be reserved for patients with a history of myocardial infarction and/or a basal left ventricular dysfunction, in whom assessment of myocardial viability is of major interest. Extensive clinical validation of the dual-isotope procedure is required and optimal acquisition and reconstruction parameters should be established.