Brain insulin receptor and insulin-like growth factor I (IGF-I) receptors are similar to their peripheral, non-neural counterparts, being comprised of two alpha subunits and two beta subunits in a heterotetrameric formation. However, they have smaller apparent Mr compared to the peripheral receptors on sodium dodecylsulfate- polyacrylamide gel electrophoresis. These unique insulin and IGF-I receptors have been studied in membranes prepared from whole retina, brain, peripheral nerves, as well as from neural-derived cultured cells. Primary cultures of neuronal cells contain unique insulin and IGF-I receptors resembling those of whole brain. Peripheral nerves and glial cells on the other hand, contain insulin and IGF-I receptors similar to those found in non-neural tissues. In intact cells both insulin and IGF-I receptors undergo ligand- induced auto-phosphorylation as well as phosphorylation of endogenous substrates. Neuronal and glial cells in primary culture demonstrate rapid receptor autophosphorylation. NG 108, a neuroblastoma cell line, in addition to receptor phosphorylation demonstrates phosphorylation of an endogenous substrate phosphoprotein (pp 185) of Mr 185kDa. Both insulin and IGF-I induce phosphorylation of their receptors and pp 185 on tyrosine residues. Thus neural-derived cells express functional insulin and IGF-I receptors, and are model systems for studying insulin and IGF-I action on the nervous system.