The bromination of silk fabrics was studied under heterogeneous conditions in N,N-dimethylformamide using three reagent systems, molecular bromine, methanesulfonyl bromide (MsBr), and N-bromosuccinimide (NBS)-triphenylphosphine (PPh3) in combination with sodium bromide. Molecular bromine brominated tyrosine residues selectively and consecutively to 3-bromotyrosine and 3,5-dibromotyrosine residues. MsBr reacted only with serine residues to give 3-bromoalanine (Br-Ala) residues. The addition of sodium bromide to the NBS-PPh3 system suppressed the bromination of tyrosine residues and slightly increased the yield of Br-Ala residues.