A patient with severe progressive neuropathy and growth retardation who showed a persistent ketosis despite normal blood glucose levels is described. A liver biopsy was analyzed for 3-oxoacyl-CoA thiolase activity. One of the mitochondrial 3-oxoacyl-CoA thiolases which in normal control liver could be activated by K+ was virtually absent in the patient's liver. An intensive search for 3-methylhydroxybutyric acid and 3-methylacetoacetic acid by gas chromatography/mass spectroscopy in the patient's urine failed to show the presence of these acids, demonstrating that the 3-methylacetoacetyl-CoA thiolase is functioning in this patient. It is therefore concluded that the persistent ketosis is due to a deficiency of the mitochondrial acetoacetyl-CoA specific thiolase.