The carbohydrate-deficient glycoprotein syndromes are a recently delineated group of genetic, multisystemic diseases with major nervous system involvement. Three distinct variants have been recognized and there are probably many more. They are characterized by a deficiency of the carbohydrate moiety of secretory glycoproteins, lysosomal enzymes and probably also membranous glycoproteins. The biochemical changes are most readily observed in serum transferrin and the diagnosis is usually made by isoelectric focusing of this glycoprotein. The deficiency of sialic acid, in particular, results in a cathodal shift and hence the presence of abnormal isoforms of transferrin with higher isoelectric points than normal. The basis defects are probably in the processing and synthesis of the carbohydrate moiety of glycoproteins; there is indirect evidence for a deficiency of asparagine-N-linked oligosaccharide transfer in type I (endoplasmic reticulum defect) and for a deficiency of N-acetylglucosaminyltransferase II in type II (Golgi defect). From the large number of patients detected in only a few years, it is expected that these diseases will become as important as, for example, the lysosomal, peroxisomal or mitochondrial disorders. Their study will undoubtedly yield a wealth of new information on the function of glycoproteins and of their carbohydrate moiety.