Spreading cortical depression induced by the topical application of 25 % KC1 onto on hemisphere of the rat brain produced an increase in 32P radioactivity in the proteins of the microsomal [+39 %] and membrane [+21 %] fraction of the affected hemicortex compared with the intact contralateral hemicortex; conversely, radioactivity in the cytosol fraction fell by 19 %, while in the mitochondrial fraction it remained the same. The results are evaluated from the aspects of a possible difference in the response of cAMP-dependent and cAMP-independent protein phosphorylation to the depolarization of cortical cells in vivo.