The effects of a single vs repeated bouts of exhaustive exercise on myocardial integrity were evaluated in the rodent. Rats were randomly divided into three groups: a sedentary control, single swim-to-exhaustion, and seven consecutive daily swims-to-exhaustion groups (n = 5 in each group). Overall morphology was evaluated histologically and sarcolemmal (SL), sarcotubular (ST), and mitochondrial (MITO) membranes were examined ultrastructurally using transmission electron microscopy. Neither single nor repeated bouts of exhaustive exercise produced myocardial hypoxia, as assessed by MITO morphology. However, increased interstitial space as well as significant swelling (P less than 0.01) was observed in ST from both 1- and 7-day exhausted animals. These findings were not observed at all in control myocardium. Higher magnification (x 45,000) in some instances revealed whole disruption of sarcotubular membranes in myocardium from swim-exhausted animals. The incidence of membrane disruption was higher (P less than 0.01) in 7-day vs 1-day swim-exhausted groups and not observed at all in control rats. Although in no instance did we observe disruption of SL membranes, their convoluted nature in myocardium from both exercised groups indicated exhaustion-induced fluid and/or ionic shifts within the left ventricle. These findings provide a structural basis for the reduction in myocardial sarcoplasmic reticulum and MITO Ca++ uptake previously observed following repeated bouts of exhaustive exercise.