The distribution of serum cobalamin-binding proteins was studied in 30 patients with low-grade multiple myeloma and in 26 patients with high-grade myeloma. The mean total cobalamin concentration (holotranscobalamin I and II) was similar in both groups of patients. We found a marked rise in total unsaturated binding cobalamin capacity mainly due to an increase in apotranscobalamin II (apo-TC II) in patients with high-grade myeloma. There was also a positive correlation between serum beta-2-microglobulin (B2M) and apo-TC II in myeloma patients. Our results indicate that pretreatment measurement of serum apo-TC II could supplement B2M as a prognostic guide.