The genetic polymorphism of the vitamin B12 transport protein transcobalamin II (TC II) was studied in the Caucasian population and in families. There are five codominent alleles of TC II which show a Mendelian mode of inheritance. No genetic linkage of TC II was found with gene loci for ADA, GLO I, Pi, HLA, AB0 and AK1. TC II like proteins could be detected on autoradiograph of PAGE in two patients with congenital homozygosity for functional TC II deficiency. These vitamin B12 binding proteins in the patients' serum were shown not to be normal R-proteins.