A study was undertaken to determine if sustained administration of isoproterenol (ISO) alters biochemical and functional properties of hearts and the submaximal and maximal exercise capacity of rodents. Compared to sham-treated controls of the same age, sex and body weight, 4 wk of ISO (0.2-0.4 mg/kg s.c.) produced an .apprx. 30% increase in combined ventricle wet weight (P < 0.001). Respiratory capacity of homogenates, total muscle protein concentration, and actomyosin and myofibril ATPase of heart muscle of the ISO-treated group were the same as in the control group. Various cardiac function parameters in situ, obtained under control conditions and in response to tyramine-induced norepinephrine release, were similar for the 2 groups. ISO-treated rats had slightly greater endurance for running submaximally on a treadmill than the control rats (P < 0.10), but their maximal capacity to utilize O2 (.ovrhdot.VO2 max) was not different from controls. Apparently, rodent hearts moderately enlarged by relatively low doses of isoproterenol possess normal metabolic and functional capacity. This cardiac enlargement had no apparent effect on maximal exercise performance of the whole animal.