MEASUREMENTS of the surface area accessible to solvent provide a convenient definition of the surface and the inside volumes in proteins of known X-ray structure. The study of the accessibility to solvent of amino acid residues in several proteins1-3 has confirmed the early observation that polar residues are found mostly on the surface and non-polar residues mostly inside globular protein structures. But the accessibility shows systematic variations with the molecular weight, because of the change in surface to volume ratio. Experimental data4 indicate that the accessible surface area A (in Å2) of monomeric globular proteins follows the law5,6: which implies that the mean accessible surface area per residues decreases like M -1/3 (where M is molecular weight) with increasing M, from about 68 Å2 for proteins of 6,000 molecular weight to 38 Å2 for proteins of 35,000 molecular weight. Thus, the accessibility to solvent is not a characteristic of the amino acids.