Recent work in the laboratory has shown the presence of many neuron-specific phosphoproteins in the mammalian nervous system. Two of these proteins, Protein III and Synapsin I, are specifically associated with synaptic vesicles in neurons throughout the brain. Protein III consists of two polypeptides, Protein IIIa (Mr 74 kD) and Protein IIIb (Mr 55 kD). These two polypeptides have similar chemical immunological and biological properties and they seem to be closely related to Synapsin I which also consists of two polypeptides, Ia (Mr 86 kD) and Ib (Mr 80 kD). Protein III and Synapsin I may play roles in synaptic function as their states of phosphorylation are increased by agents that depolarize neuronal membranes, by 8-bromoadenosine 3':5'-monophosphate (cAMP), and by several neurotransmitters, including dopamine, serotonin and norepinephrine (4, 5, 9, 11). In the present study, the authors investigated Protein III and Synapsin I in human brain tissue obtained at autopsy from normal individuals and from individuals suffering from a variety of diseases affecting the central nervous system.