Abstract A family of six with three male children affected with the cerebro-oculo-renal syndrome has been studied for a specific biochemical abnormality in amino acid metabolism. Oral administration of the single amino acids l-lysine, l-hydroxyproline and l-glycine did not affect the urinary amino acids excreted by the oldest affected boy. In contrast, ingestion of a comparable amount of l-ornithine resulted in intensification of the abnormal urinary amino acid pattern. Feeding the parents and sister equimolar amounts of ornithine resulted only in the mother in an abnormal urinary pattern of amino acids which resembled that of the affected male children. The data are consistent with a sex-linked mode of inheritance in this family. The syndrome described herein probably represents a variant of the cerebro-oculo-renal syndrome as originally described by Lowe.