The urea cycle is a series of six reactions necessary to rid the body of the nitrogen generated by the metabolism, primarily of amino acids, from the diet or released as the result of endogenous protein catabolism. Arginase is the sixth and final enzyme of this cycle. Arginase catalyzes the conversion of arginine to urea and ornithine, the latter recycled to continue the cycle. Hyperargininemia due to arginase deficiency is inherited in an autosomal recessive manner and gene for arginase, designated AI, has been cloned. Unlike the other urea cycle enzymes, a second gene encoding arginase, with similar structural properties and enzyme characteristics, exists and has been named Arginase II (AII). Comprehensive histories and physical examinations confirm a strikingly uniform clinical picture and one notably different from patients with other urea cycle disorders. This condition rarely presents in the neonatal period and first symptoms typically present in children between 2 and 4 years of age. First symptoms are often neurologically based. If untreated, symptoms are progressive with a gradual loss of developmental milestones. With adherence to a dietary and drug regimen, a favorable outcome can be expected, with cessation of further neurological deterioration and in some instances, of improvement. This article summarizes the clinical course of selected patients who represent the full spectrum of presentations of arginase deficiency. In addition to the clinical characterization of this disorder; the biochemical, enzymatic, and molecular evidence of disease is summarized. Treatment and prenatal diagnosis are also discussed.