Homocarnosinosis, an inherited disorder, is characterized by an elevated level of the dipeptide homocarnosine (Hca) in the CSF and the brain and, in addition, by carnosinuria and serum carnosinase deficiency. In three children with homocarnosinosis the biochemical aberration co-exists with paraplegia, retinitis pigmentosa, and a progressive mental deficiency. In the mother, however, only the biochemical aberration was present without clinical symptoms. In order to study whether this elevated level of Hca and increased excretion of carnosine (Car) could be reduced towards normal, a dietary regiment with restriction of histidine (His) was maintained for nearly 2 1/2 years for two of the patients, 33 and 39 years old, with homocarnosinosis associated with neurological symptoms. His was reduced by about 90% in the CSF, in the plasma and in the urine. Within 5-6 months CSF Hca was reduced by about 70%, and urinary Car by 22 and 42%. The clinical neurological symptoms, however, did not alter significantly together with these biochemical changes.