The present study was designed to establish a) whether chromaffin cells of the human adrenal medulla express immunoreactivity for beta-amyloid precursor protein (beta APP) and/or beta-amyloid protein (beta/A4); and b) whether cells expressing one or both of the above-mentioned proteins display immunoreactivity for the low- (gp75) and/or the high-affinity (gp140-trkA) nerve growth factor receptor. To identify chromaffin cells and their supporting cells, chromogranin A, neurofilament proteins, and S-100 protein were studied in parallel. Beta APP and beta/A4 immunoreactivity (IR) was observed primarily labeling two different cell populations, without colocalization: Beta APP IR was found in the adrenal cortical cells, which were mainly localized in the reticulate layer and in the blood vessel walls, whereas beta/A4 IR was observed in the chromaffin cells. Furthermore, supporting cells were also immunoreactive for beta/A4, and sympathetic ganglionic cells were immunoreactive for both beta APP and beta/A4. Interestingly, clusters of cells expressing beta/A4 IR also displayed gp 75 IR and/or gp140-trkA IR. Finally, all chromaffin cells (identified by chromogranin A IR) were immunolabeled for the 200 kDa neurofilament subunit, but not for a phosphorylated epitope of this protein. These results demonstrate the occurrence of beta/A4 IR, but not of beta APP, in the chromaffin cells of the human adrenal gland. The complementary distribution of amyloid-related proteins, and the possible involvement of neurotrophins in beta/A4 metabolism are discussed.