The nature of the interaction between serum proteins and a number of food colourings was investigated by electrophoresis on cellulose acetate strips and polyacrylamide gel and by filtration through a Sephadex gel column. Electropherograms on cellulose acetate showed no migration of Rhodamine B and Rhodamine 6G, separation of Violamine R into two components as it migrated, and migration of all other colourings towards the anode in a single band. During electrophoresis, the complexes between serum proteins and Fast Green FCF, Patent Blue V, Blue VRS, Brilliant Blue FCF, Light Green SF Yellowish, Green S, Rhodamine 6G, Rhodamine B, Violamine R, fluorescein, Sunset Yellow FCF, Black PN and Black 7984 separated into their component colouring and protein fractions, the mobilities of which were unaffected by the interaction. The protein complexes formed by Eosine G and amaranth appeared to be unaffected by electrophoresis on cellulose acetate strips but readily separated on polyacrylamide gel. The complexes formed by erythrosine and by Violets 6B, 5BN and BNP were not separated by electrophoresis on either medium but could be separated by filtration on Sephadex gel. These studies indicate that the electrostatic bond between protein and colourings may be relatively firm, resisting separation of the components by electrophoresis, or so weak as to dissociate easily in an electrophoretic field. The formation of a complex held together by strong forces results in delayed absorption of the dye from sc injection sites and influences the local tissue produced. The latter development also depends on the surface activity, lipophilic character, and certain other physical properties of the colouring. The nature of the local tissue reactions to short-term courses of sc injections of Violet 6B, 5BN and BNP strongly suggests that the sarcomas previously elicited by Violet 6B in the rat are attributable to repeated trauma and regeneration, rather than to chemical carcinogenesis.