The contribution of heat shock protein 72 (HSP72) to the protection of cardiac function was examined in rats with chronic heat failure (CHF) following coronary artery ligation (CAL). The CAL animals revealed functional deterioration without low cardiac output 2 wk after CAL and with low cardiac output 8 wk after CAL, suggesting that CHF had developed by 8 wk after CAL. The hearts isolated from animals 2 and 8 wk after CAL (2-wk CAL heart and 8-wk CAL heart, respectively) were subjected to hyperthermia (at 42°C) for 15 min, followed by 6-h perfusion (hyperthermia/6-h perfusion). The 2-wk CAL heart showed a 19.0 ± 3.9% decline in the rate- pressure product (RPP) after hyperthermia/6-h perfusion, similar to the nonoperated control (19.8 ± 2.9% decline). The production of myocardial HSP72 increased in the 2-wk CAL heart in response to hyperthermia (412.7 ± 29.5% of each prehyperthermia value). The 8-wk CAL heart showed a reduction in the RPP (45.2 ± 4.3% decline) after hyperthermia/6-h perfusion, associated with blunting of the production of HSP72 (68.9 ± 22.6% increase, respectively). The results suggest that functional deterioration of the isolated failing heart may be attributed to a reduction in the production of myocardial HSP72.