1. Dynorphin, an endogenous opioid peptide, acts on specific kappa-opioid receptors in the rat heart for the local regulation of atrial natriuretic peptide release. No known study has examined the expression of dynorphin in the human heart. 2. In the present study a specific radioimmunoassay technique was used to determine ventricular expression of dynorphin at the peptide level in endomyocardial biopsy specimens and in plasma obtained from 13 heart transplant recipients. Ventricular biopsy specimens collected from 10 patients without cardiac complications during necropsy (less than 24 h from time of death) and plasma samples from 10 normal healthy subjects were used as controls. 3. The immunoreactive level of ventricular dynorphin was higher in heart transplant recipients (mean +/- SEM 141 +/- 32 pg/mg of soluble protein, range 7-573 pg/mg of soluble protein, P < 0.001) than in control subjects (16 +/- 3 pg/mg of soluble protein, 2-34 pg/mg of soluble protein). The plasma concentration of immunoreactive dynorphin was also higher (P < 0.001) in heart transplant recipients (mean +/- SEM 14 +/- 1 pg/ml, range 5-39 pg/ml) than in normal healthy subjects (7 +/- 0.4 pg/ml, 5-10 pg/ml). No relationship was observed between ventricular and plasma levels of dynorphin. 4. These results show that immunoreactive levels of dynorphin in plasma and ventricle are increased after heart transplantation, suggesting a possible pathophysiological role for dynorphin in the heart.