Protein A is a cell-wall constituent from Staphylococcus UUI~W [ 1,2] with the ability to react with nonimmune immunoglobulins from several mammalia [3,4]. The active binding site for protein A is situated in the Fc-region of human IgCl, IgG2 and IgG4 [ 561. As a consequence of the reaction, the complement system, for instance, is activated, as well as certain immunological reactions are initiated in vivo [7-91. Tyrosine-modifying reagents inhibit the reactivity of protein A, as shown by nitration, acetylation and iodination [lo121. The circular dichroism (CD) spectrum of protein A is very characteristic with strong, well separated bands at 261 and 268 nm originating from the phenylalanine residues [ 131. The conditions to detect changes of the intrinsic Cotton effects resulting from the protein A-IgG interaction can therefore be considered as relatively good, especially as an isolated Fc-fragment can be used instead of the complete y-globulin. Thereby, the ellipticity background from the non-reacting Fab-fragments can be avoided, which means that any specific conformational changes can be detected more easily. The present paper describes the CDchanges seen, when protein A interacts with the Fc-fragment of a human myeloma protein.