The regulation of the state of phosphorylation of protein I, a specific neuronal protein that appears to be associated predominantly with synaptic vesicles, has been studied in intact sections of bovine superior cervical ganglion. For this purpose, a technique was developed that made possible the quantitation of the state of phosphorylation of as little as 5 fmol of protein I. Incubation of ganglion sections in the presence of dopamine, 8-bromo-cyclic AMP, or depolarizing agents (i.e., high K+ concentration or veratridine) increased the state of phosphorylation of protein I relative to that of control ganglion sections. Other results indicated that the effect of dopamine is probably mediated via the activation of a cyclic AMP-dependent protein kinase and that the effect of high K+ concentration is probably mediated via the activation of a calcium-dependent protein kinase.