Cultured heart cells from adult rats were exposed to anoxia in a substrate-free Tyrode's solution at constant pH. In this system the metabolic and the morphologic pattern can be investigated simultaneously. Anoxic changes develop gradually above 2 mumol adenosine triphosphate (ATP)/ gww . Morphometry reveals that the morphologic changes are closely related to the energetic state: creatine phosphate (CP) decay is accompanied by the loss of small mitochondrial matrix granules (r = 0.97). The fall of ATP is coincident with sarcomere shortening (r = 0.95) and, below 4 mumol/ gww , with mitochondrial swelling (r = -0.88). The number of lipid droplets correlates with the ATP level during anoxia and reoxygenation (r = -0.92). The early energetic depletion is accompanied by a moderate release of cytosolic enzymes and morphologic changes: the appearance of sarcolemmal microblebs and an increase in subsarcolemmal vesicles. Below an average ATP level of 2 mumol/ gww an increasing number of individual cells fail to recover when reoxygenated . However, that failure is accompanied neither by massive enzyme release nor by ultrastructural damage regarded as typical for the "oxygen paradox."