Crystallographic and theoretical (ab initio) data on intermolecular nonbondedinteractions have been gathered together in a computerised library(’IsoStar‘). The library contains information about the nonbonded contactsformed by some 250 chemical groupings. The data can be displayed visually andused to aid protein–ligand docking or the identification of bioisostericreplacements. Data from the library show that there is great variability inthe geometrical preferences of different types of hydrogen bonds, although ingeneral there is a tendency for H-bonds to form along lone-pair directions.The H-bond acceptor abilities of oxygen and sulphur atoms are highly dependenton intramolecular environments. The nonbonded contacts formed by manyhydrophobic groups show surprisingly strong directional preferences. Manyunusual nonbonded interactions are to be found in the library and are ofpotential value for designing novel biologically active molecules.