The results of biochemical and immunological characterization of five electrophorctic variants of human serum ceruloplasmin in Negroes are described. The variants were found to differ in the surface charge of the protein moeities of their molecules. No difference in their molecular weights could, however, be ascertained. The specific activities of the variants were strictly similar. Compared to the normal form CpB, CpA is more resistant and Cp Bpt is more susceptible to inhibition by either cyanide or azide of their oxidase activity while CpNH and CpA appear to resemble CpB in this regard. Citrate exerts uniform inhibition on all variants.Based on the differences in susceptibility to inhibition, the relative concentration of CpA to CpB protein in the CpAB heterozygote has been estimated to be 2:1. This may indicate that alleles at the ceruloplasmin locus (Cp) determine ceruloplasmin synthesis with different efficiencies. However, except for the Cp Bpt variant, the total level of ceruloplasmin protein in the serum appears to be regulated by a mechanism independent of the Cp phenotype and extrinsic to its structural genes.The objectives of these studies have been (A) to establish the distinctiveness of ceruloplasmin variants, (B) to provide means of identification and definition of new variants which may not differ electrophoretically from each other or from the variants already described, e.g. through differences in their inhibition profile, (C) to gather and assemble the necessary information to construct a model for control of quantitative expression of ceruloplasmin protein.