Objective: To study the expression of adrenomedullin, a potent vasodilator peptide originally isolated from a pheochromocytoma, in ectopic ACTH-secreting tumors. Methods: Tumor tissue concentrations of adrenomedullin, calcitonin gene-related peptide, neuropeptide Y, endothelin- 1, corticotropin-releasing hormone and ACTH were measured in three ectopic ACTH-secreting tumors by RIA. The expression of adrenomedullin mRNA was examined by northern blot analysis of tissue from one of the tumors. Results: Immunoreactive adrenomedullin was detected in tumor tissues of three ectopic ACTH-secreting tumors (0.60-18.5 pmol/g wet weight). Calcitonin gene-related peptide, neuropeptide Y, endothelin-1 and corticotropin-releasing hormone were also detected in the tumor tissues. The tumor tissue concentrations of immunoreactive adrenomedullin were comparable to those of these four peptides, but much lower than those of ACTH. Northern blot analysis showed the expression of adrenomedullin mRNA in one tumor from which sufficient tissue was available for such study. The plasma concentration of immunoreactive adrenomedullin was increased in one patient (41.3 pmol/l, control 13.5 ± 3.6 pmol/l, mean ± S.D., n = 12). Conclusions: These results suggest that adrenomedullin is produced by ectopic ACTH-secreting tumors, together with other neuropeptides, and raise the possibility that adrenomedullin is related to the pathophysiology of these tumors.