Pharmacologic and immunologic evidence suggests that nitric oxide-coupled mu-subtype opiate receptors are expressed in human vascular endothelium. In this study, we present molecular evidence of mu opiate receptor expression. Using primers derived from the human neuronal mu1 opiate receptor, we used RT-PCR to detect expression of mu transcripts from human endothelia. Sequence analysis of the RT-PCR products revealed 100% identity with the neuronal human mu1 receptor. We further show that pretreatment of human internal thoracic artery and cardiac atrial endothelium with the proinflammatory cytokines interleukin-1-alpha and -beta led to a significant increase in both the expression of the mu transcript and in morphine-stimulated nitric oxide release measured amperometrically. Taken together, these studies provide molecular evidence that mu-type opiate receptors are expressed in human vascular endothelia and that their expression can be upregulated by proinflammatory cytokines.