Literature on sparse-fur (spf) mutant mouse, as an animal model of congenital hyperammonemia has been reviewed earlier^l,4. Our current estimates indicate that over one hundred full-fledged articles have been published on spf mice since 1976, when the X-linked hepatic ornithine transcarbamylase (OTC; E.C. 2.1.3.3.) deficiency associated with the sparse-fur mutation was described for the first time⁵. An allelic form, the spf^ash (abnormal skin and hair) mutation, having a somewhat different phenotype to spf mouse, was also shown to have a quantitative deficiency of the hepatic OTC⁶. These publications have covered various aspects of the expression of the spf gene, including the clinical pathology, neurochemical pathology, behavior, experimental carcinogenesis and pharmacogenetics. Moreover, the spf mouse is now established as an animal model to study the effects of transgenic and viral-mediated gene therapy^7,12. As indicated in Figure. 1, this has brought in a dramatic increase in new research studies on the spf and spf^ash mice, a big majority of which were initiated from our laboratory. It can be said that the spf mouse is now established as the most appropriate model to study the pathology and therapy of chronic hyperammonemic encephalopathy, particularly of hereditary origin. In the following text, we shall briefly review the nature and expression of the spf mutation, at the hepatic and intestinal levels, and its similarity to the human OTC deficiency. Particular emphasis shall be given to the neurochemical pathology in the spf mouse, from the point of view of metabolic and neurotransmitter abnormalities.