There is evidence that peptides related to alpha-melanocyte-stimulating hormone (alpha-MSH) are involved in regulating the zona glomerulosa of the adrenal cortex in certain species. We have investigated the amount of immunoreactive (IR)-alpha-MSH in the human pituitary gland of patients suffering from Addison's disease. We show increased numbers of cells containing demonstrable IR-alpha-MSH in the anterior lobe in these patients. Using an antiserum with specificity for the acetylated N-terminus of alpha-MSH we suggest that the major form present is desacetyl-alpha-MSH. These findings are in keeping with a role for anterior lobe derived desacetyl-alpha-MSH in the regulation of the human adrenal cortex.