With a polysaccharide microsphere suspension (Sephadex), coronary flow of isolated perfused rat hearts was reduced by approximately 70%. During this Sephadex-induced ischemia, the energy charge and creatine phosphate content of the myocardial tissue dropped significantly, while total nucleoside and lactate release from the heart increased. During hypoxia (30% O2), changes in high-energy phosphate content and lactate and nucleoside release were similar to the changes induced by ischemia. During hypoxia, coronary flow rate was increased by 47%. Thus, Sephadex-induced reduction of coronary flow could be a useful model in studies of metabolic change during ischemia.