A study of some sulfonylureamolecules with consideration of watermolecules as its solvent was undertaken. The influence of the water molecules on the structure-activity relationship of the 35 sulfony-lurea molecules was discussed. By supper-imposition of structural sulfonylmolecules, a molecular RM S was correlated with p I 50, which denotes that the configuration difference in water solution is one of the reasons which causes the difference in bioactivity.