Recent studies of the human brain insulin receptor raise the possibility that some of the differences described between rat brain insulin receptors and rat liver insulin receptors may have been due to the presence of insulin-like growth factor I (IGF-I) receptors in the brain. This study details side by side comparison of the alpha-subunits from insulin and IGF-I receptors in rat brain and liver. Insulin and IGF-I receptors are present in rat liver and brain, although IGF-I receptors are at a very low concentration in rat liver. These insulin and IGF-I receptors are clearly separate entities based on relative ligand affinities, antigenicity, and apparent molecular size. The alpha-subunits of the brain receptor for both insulin and IGF-I are about 10K lower in molecular size than the corresponding alpha-subunits from liver. These brain alpha-subunits are less sensitive to neuraminidase digestion than the corresponding liver alpha-subunit, although they do bind to wheat germ agglutinin. After treatment with endoglycosidase-F the deglycosylated apoproteins for both receptors from liver and brain have similar mol wt, suggesting that the observed differences were due to differences in N-linked glycosylation. The significance of differences in N-linked glycosylation between the brain receptors for insulin and IGF-I and the corresponding receptors in liver is not known.