A radioimmunoassay has been developed for measuring protein I, a basic, neuron-specific protein associated with nerve terminals. The procedure utilizes the detergents NaDodSO4 and Nonidet P-40 to prevent nonspecific adsorption of this highly charged protein to various surfaces. By use of this procedure, it has been possible to show that protein I comprises approximately 0.4% of the total protein in cerebral cortex of several mammalian species. In addition, the amount of protein I was determined in about 40 regions of cat brain. The results suggest that measurement of protein I may provide a quantitative method for estimating the density of nerve terminals in various regions of the mammalian nervous system.