Perfusion of the isolated intact rat heart with Krebs-Henseleit solution containing agonists ((-)-TAN-67, DPDPE, and dalargin) or antagonists of delta-opioid receptors (naltrindole, TIPP[psi], and ICI 174,864) in a final concentration of 0.1 mg/liter was followed by a decrease in the heart rate, end-diastolic pressure, contraction rate, relaxation rate, and left ventricular developed pressure. Perfusion with a solution containing the delta-opioid receptor agonist DPDPE or delta-antagonists naltrindole, TIPP[psi], and ICI 174,864 before modeling of global ischemia increased the severity of reperfusion-induced contractile dysfunction in the myocardium. Our results suggest that delta-opioid receptor antagonists in vitro exhibit properties of partial delta-receptor agonists.