The ability of multidetector computed tomography (MDCT) to detect stress-induced myocardial perfusion abnormalities is of great clinical interest as a potential tool for the combined evaluation of coronary stenosis and its significance. However, stress testing requires repeated scanning, which is associated with additional radiation exposure and iodine contrast. Our goal was to determine the effects of reduced tube voltage and contrast dose on the ability to detect perfusion abnormalities. We studied 40 patients referred for CT coronary angiography (CTCA). Images were acquired at rest and during regadenoson stress (256-channel scanner, Philips) using 120kV tube voltage with 80-90 ml contrast in 20 patients and 100kV with 55-70 ml contrast in the remaining 20 patients. Custom software was used to define 3D myocardial segments and measure segmental x-ray attenuation. In each group of patients, myocardial attenuation was averaged for segments supplied by arteries with stenosis causing >50% narrowing on CTCA, and separately for segments supplied by arteries without significant stenosis. In both groups, myocardial attenuation was equally reduced in segments supplied by diseased arteries, despite the 74% reduction in radiation and the 28% reduction in contrast. Regadenoson stress MDCT imaging can detect hypoperfused myocardium even when imaging settings are optimized to provide a significant reduction in radiation and contrast doses.