A 44-year-old man suffered from repeated impairment of consciousness associated with flapping tremor, myoclonus and generalized convulsions, and died in coma 6 months after admission. He had had a psychosomatically underdeveloped childhood, with a propensity for legumes without a family history of the same or a record of consanguinity. On admission, he had disturbed consciousness and emaciation without other physical abnormalities. The EEG revealed diffuse slow waves with occasional appearance of triphasic waves. A high level of serum citrulline (534.7 nmol/ml) was recognized and the assay of urea cycle enzymes in the liver demonstrated decreased argininosuccinate synthetase (ASS) activity (0.062 U/g liver, 7.4% of that in normal liver), although no kinetic abnormality was found. Accordingly he was diagnosed as having type II citrullinemia. In addition, this case could be classified as cluster type of localization of the ASS in the liver by immunohistochemical study. There were characteristic findings concerning his clinical picture and laboratory data, such as a significant correlation between the grade of disturbed consciousness and arterial blood gas pH (r = 0.61, p less than 0.01). However, the blood ammonia level did not always correlate with the severity of disturbed consciousness. Oral treatment with sodium citrate and sodium benzoate was very effective, though transiently, for disturbed consciousness in this case. Pathological findings of the autopsied liver were fatty change and fibrosis. Neuropathologically, characteristic findings were brain edema with cerebellar tonsilar herniation, laminar necrosis with spongy formation in cerebral cortex, and Alzheimer type II glia. The relationship between citrullinemia and other hepatic encephalopathy was also discussed.