Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder manifested by parkinsonism and dysfunction of autonomic, cerebellar, urinary, and pyramidal systems. The most frequent presentation is with a combination of parkinsonism and autonomic dysfunction, but cerebellar ataxia with autonomic failure occurs frequently as well. Striatonigral degeneration (SND) and sporadic olivopontocerebellar atrophy (sOPCA) can progress to include autonomic failure and thus may be forms of MSA, but it is not known whether all such cases progress to MSA. Utilizing positron emission tomography (PET) with various ligands, my colleagues and I have investigated the biochemical changes in sOPCA and MSA to understand the relationship between these disorders. An initial study revealed decreased local cerebral metabolic rates for glucose in the brainstem, cerebellum, putamen, thalamus and cerebral cortex in both MSA and sOPCA, suggesting that many sOPCA patients would evolve to develop MSA. Later studies confirmed this by demonstrating decreased monoaminergic nigrostriatal terminals in both sOPCA and MSA patients. The studies suggest that the ligand used might be helpful in determining the risk that an individual patient with sOPCA will progress to develop MSA. An investigation of the course of sOPCA patients observed clinically over several years revealed that approximately one-fourth of them progress to MSA within five years. Studies of gamma-aminobutyric acid type A/benzodiazepine neurotransmitter receptors revealed that these sites are largely preserved in sOPCA and MSA, indicating that symptomatic pharmacological therapy may be possible in these disorders.