The six hour stress in rats was modeled by the method of O. Desiderato. Cardiac damage was estimated by myocardial uptace of radioactive 99Tc-pyrophosphate. Intravenous administration of mixed mu and delta opioid receptor agonist, D- Ala2, Leu5, Arg6-enkephalin (dalargin), (non-penetrating through the blood brain barrier) at a dose of 0.1 mg/kg before stress decreased stress-induced 99Tc-pyroposphate uptake. Pretreatment with dalargin completely abolished the stress-induced increase in conjugated dienes and malondialdehyde levels in myocardium and prevented a decrease in total lipid soluble antioxidant levels in the heart after stress exposure. Stress is accompanied by an increase in activity of catalase, glutathione peroxidase, glutathione reductase and a decrease in activity of superoxide dismutase (SOD). Pretreatment with dalargin completely reversed stress-induced decrease in SOD activity but had minor effect on the activity of other antioxidant enzymes. Stress also resulted in an increase in myocardial content of thromboxane and a decrease in prostacycline and prostaglandin E levels in the heart. Pretreatment with dalargin completely eliminated these stress-induced changes in myocardial prostanoid levels. We propose that stress-induced heart injury depends on the activation of lipid peroxidation processes and changes in the prostanoid levels in the heart. Cardioprotective effect of dalargin during stress may be mediated via peripheral mu and delta opioid receptor stimulation and an inhibition of lipid peroxidation processes through SOD activation and also a recovery, of normal prostanoid levels in the heart.