This study was designed to examine the ability of color-labeled microspheres to depict different states of myocardial perfusion in a rabbit model of ischemia-reperfusion. A thread was passed under the left anterior descending artery (LAD) and the first left marginal artery of anesthetized New Zealand White rabbits. Blue-labeled microspheres (500/g body wt) were injected into the left atrium. The thread was tightened in rabbits belonging to the experimental group (n = 8), and red-labeled microspheres (500/g body wt) were injected. The snare was loosened, and yellow-labeled microspheres (500/g body wt) were injected before (n = 5) or after (n = 3) methylene blue injection. In animals belonging to the “sham” group (n = 4 and n = 2, respectively), the sequence of injections was similar, but the snare was not tightened. The animals were euthanized, and 0.3-1 g sections were cut from ischemic and nonischemic regions, as determined by methylene blue in the experimental subgroups and from the corresponding regions in the “sham” subgroups. The tissue samples were digested with 4 M KOH, ethanol 70%, and ultrasonication, and the microspheres were recovered by vacuum filtration. The dye was chemically removed from the microspheres, and the photometric absorption of each sample was determined. There was no significant difference between the experimental and “sham” groups in baseline uptake of blue-labeled microspheres. Rabbits belonging to the experi mental subgroups had significantly lower mean uptake of red microspheres during ischemia relative to “sham” (0.51 ±0.08 vs 1.06 ±0.24 and 0.36 ±0.19 vs 0.91 ±0.12, respectively). After loosening of the snare there was no difference in uptake of yellow- labeled microspheres. Color-labeled microspheres depict myocardial ischemia in the rabbit. The ability of color-labeled microspheres to depict reperfusion hyperemia remains to be proved.