The formation of the protein-protein interface by the insulin dimer, the trypsin-PTI complex and the alphabeta oxyhaemoglobin dimer removes 1,130-1,720 A2 of accessible surface from contact with water. The residues forming the interface are close packed: each occupies the same volume as it does in crystals of amino acids. These results indicate that hydrophobicity is the major factor stabilising protein-protein association, while complementarily plays a selective role in deciding which proteins may associate.