The clinical data and the imaging findings of the positron emission tomography (PET) and the magnetic resonance imaging (MRI) studies in five patients, previously diagnosed to have propionic acidemia, were retrospectively reviewed. The patients were all normal at birth. The first clinical signs, typically hypotonia and failure to thrive, appeared during the first 2 years of life. With progression of the disease, the neurological findings consisted of variable degrees of dementia and extrapyramidal symptoms, notably dystonia, choreoathetosis and rigidity of variable degrees. Initial cerebral PET and MRI studies were normal. Follow-up MRI examinations showed progressive basal ganglia degeneration, with evidence of atrophy and signal abnormalities within the caudate nuclei and the putamina. The thalamic structures were normal. The PET studies demonstrated increased uptake in the basal ganglia and thalami, followed by decreased uptake in the basal ganglia at a later stage of the disease. The structural (MRI) and the functional (PET) studies of the brain were found to be complementary in the evaluation of propionic acidemia, and were in good correlation with the clinical findings.