Strong binding of dyes to simple globular proteins takes place predominantly in areas overlapping the binding sites for substrates, coenzymes and prosthetic groups, in preference to other regions of the protein surface. The structure of the dyes bears no obvious relationship to that of the normal ligands. It is proposed that this phenomenon is a reflection of the special stereochemical features of such sites, their hydrophobicity relative to other portions of the protein surface, and, possibly, greater flexibility in these regions of the protein molecule. The binding properties of antibodies and bovine serum albumin are discussed in relation to this apparent versatility of protein binding sites towards structurally unrelated organic ligands.