The sustentacular cells of the carotid body and the adrenal medulla of guinea pigs were studied by light and electron microscopic immunohistochemistry and compared with the Schwann or satellite cells of the peripheral nervous system. In the peripheral nervous system, neurons were immunoreactive for protein gene product (PGP) 9.5, whereas Schwann cells or satellite cells were immunoreactive for S-100 protein and vimentin. Vimentin immunoreactivity was detected on the intermediate filaments of the Schwann cells by post-embedding immunogold labeling. In the carotid body and the adrenal medulla, glomus cells or chromaffin cells were dosely enveloped by the sustentacular cells, which protruded long cytoplasmic processes and had some axons embedded in them, as in Schwann cells. The glomus cells or chromaffin cells expressed immunoreactivity for PGP 9.5, whereas the sustentacular cells expressed immunoreactivity for S-100 protein and vimentin. The sustentacular cells were characterized by the presence of abundant intermediate filaments on which immunogold particles for vimentin were densely located. From these results, it is concluded that the sustentacular cells closely resemble glial cells of the peripheral nervous system in immunohistochemical, ultrastructural, and also functional properties, and may belong to the glial lineage, originating from the neural crest.