The protein NESP55, a new member of the chromogranin family, is present in large dense-core secretory granules of neuroendocrine tissues. We investigated its cellular distribution in adrenal medulla with immunohistochemistry and in situ hybridization. A preferential co-localization of NESP55 with phenylethanolamine-N-methyltransferase in the adrenergic cell population was found by immunolabelling of consecutive sections. Noradrenergic cells also contained small amounts of NESP55, but the levels as measured by radioimmunoassay were five times lower. The distribution of NESP55 mRNA was similar to preproenkephalin mRNA which previously was shown to be confined to adrenaline-producing cells of the adrenal medulla. The present study indicates that stimulation of adrenergic cells will release significantly higher amounts of NESP55. The functional implications of this preferential secretion, however, have yet to be discovered.