Adrenomedullin is a potent vasodilator peptide that was isolated from human pheochromocytoma. But the presence of adrenomedullin in the brain has not been clarified. We studied the presence of adrenomedullin in the human brain obtained at autopsy from 6 subjects by radioimmunoassay, as well as in the human adrenal glands and tumor tissues of pheochromocytoma, ganglioneuroblastoma and neuroblastoma. Immunoreactive adrenomedullin was detected in every region of human brain examined (0.26-1.4 pmol/g wet weight) with the highest concentrations found in thalamus (1.40 +/- 0.39 pmol/g wet weight, mean +/- SEM) and hypothalamus (1.28 +/- 0.48 pmol/g wet weight). Reverse phase high performance liquid chromatography showed that the immunoreactive adrenomedullin in the human brain was eluted in the position of synthetic human adrenomedullin 1-52. High concentrations of immunoreactive adrenomedullin were found in human adrenal glands (12.6 +/- 1.0 pmol/g wet weight, n = 7), pheochromocytoma (4.5 +/- 1.5 pmol/g wet weight, n = 11), ganglioneuroblastoma (2.0 +/- 1.3 pmol/g wet weight, n = 4) and neuroblastoma (0.55 +/- 0.21 pmol/g wet weight, n = 3). The present study has shown that adrenomedullin is present in the human brain in high concentrations, suggesting that adrenomedullin acts as a neurotransmitter, neuromodulator or neurohormone in man.