Abstract Crystallized Fragment Fc of rabbit γG-globulin, prepared by digestion with papain in the presence of 0.05 m l-cysteine, dissociates into half-fragments in 0.05 m NaCl at pH 2.7. Dissociation is approximately half-complete at pH 3.1. The conditions are similar to those required for dissociation of γG-globulin into half-molecules, which supports other evidence that the noncovalent interactions between heavy chains are largely localized in Fragment Fc. Schlieren patterns, molecular weights, and results of gel filtration indicate that two subfractions, approximately equal in size, are liberated. At neutral pH, recombination of the half-fragments occurs spontaneously through noncovalent interaction. After proteolysis in the presence of a low concentration of reducing agent, the resulting crystallized Fc is largely undissociable at low pH but is rendered dissociable by further reduction and alkylation. If alkylation is omitted, after a 1-hour or 4-hour digestion with papain and cysteine, a large proportion of the Fc fragments become undissociable after removal of the reducing agent by dialysis, owing to re-formation of an interchain disulfide bond; dissociability is restored by a second reduction. Prolonged digestion with papain results in a decrease in the S-carboxymethylcysteine content of alkylated Fc fragments, and in loss of the capacity to reoxidize, if alkylation is omitted. A probable explanation is that the enzyme slowly attacks that region of Fragment Fc which contains the interchain disulfide bond.