1. 1. Human ceruloplasmin (mol. wt. = 143100; s° 20, w = 7.11 S) can be dissociated into a variety of discrete subunits by either of two kinds of treatment which increase its negative charge density. 2. 2. Exposure of ceruloplasmin to carbonate-bicarbonate buffer (pH 10.2) results in dissociation into half-molecule subunits with mol. wt. = 82500 and s° 20, w = 5.48 S, while exposure to borate-NaCl buffer (pH 12.5) results in dissociation into quarter-molecules with mol. wt. 37700 and s° 20, w = 2.63 S. In both cases the dissociation is accompanied by loss of blue color and oxidase activity and by release of prosthetic copper. This loss of “native” properties appears to be irreversible, as there is no recovery of initial color or activity upon neutralization. 3. 3. When ceruloplasmin is reacted with succinic anhydride under neutral conditions so as to modify more than 90% of the free amino groups, it dissociates into half-molecules with mol. wt. = 87900 and s° 20, w = 4.06 S. The dissociation process also results in loss of blue color and oxidase activity and in release of prosthetic copper. 4. 4. Exposure of the succinylated ceruloplasmin half-molecules to borate-NaCl buffer (pH 12.5) results in further dissociation into eighth-molecules having apparently equivalent molecular weights (17200). No new free amino groups are detectable by assay with the ninhydrin reagent, indicating that the eighth-molecule subunitsdo not arise from peptide-bond cleavage. 5. 5. The calculated values of the frictional ratio, f f 0 , for ceruloplasmin half-, quarter-, and eighth-molecules (1.87, 1.64 and 2.06, respectively) are distinctly greate than the corresponding value for native ceruloplasmin (1.48), suggesting a significant increase in asymmetry upon dissociation into subunits. 6. 6. After acrylamide-gel electrophoresis at pH 12.0, the eighth-molecule subunits are resolved into two closely spaced bands, of equal protein-staining intensity. This finding, together with the ultracentrifugal evidence, suggests equal amounts of two polypeptide chains, identical in size but differing slightly in net charge. 7. 7. Double-diffusion experiments in agar gel reveal that either type ceruloplasmin half-molecule gives a reaction of partial identity with rabbit specific anti-ceruloplasmin serum. However, neither the quarter-molecule nor the eighth-molecule gives any reaction with the antiserum. 8. 8. The simplest model for the quaternary structure of human ceruloplasmin therefore is an octamer, α 4 β 4, which may undergo sequential dissociation to produce half-, quarter- or eighth-molecules.