The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image micro and delta opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65+/-8 years old) underwent PET scanning of the chest with [(11)C]carfentanil ([(11)C]CFN) and [(11)C]- N-methyl-naltrindole ([(11)C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [(11)C]CFN or [(11)C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [(11)C]CFN and [(11)C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37+/-0.91 with [(11)C]CFN and 3.86+/-0.60 with [(11)C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [(11)C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [(11)C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function.