1. We examined the effects of naloxone (preferentially μ-antagonist), naltrindole (selective δ-antagonist) or nor-binaltorphimine (nor-BNI, selective κ-antagonist) on auricular myocardium tissue from nonfailing and failing human hearts.2. The opioid antagonists used in this study induced inhibitory effects in auricular strips from failing and nonfailing human hearts. In addition, the maximal effect, the IC 5 0 , and the slope of concentration-response curves obtained with μ-, δ-, and κ-opioid antagonists were similar in failing and nonfailing human heart tissues.3. The κ-antagonist was more effective than naltrindole or naloxone. Moreover, the IC 5 0 for nor-BNI (0.25 ± 0.01 10 - 5 M) was lower than the IC 5 0 for naloxone (26.5 ± 5.0 10 - 5 M) and naltrindole (13.8 ± 2.0 10 - 5 M). Similar results were obtained in auricular strips from failing human hearts.4. Our results demonstrate that the failing heart does not modify the inhibitory cardiac effects obtained with selective opioid antagonists.