The binding of aminobenzolamide to human carbonic anhydrase (HCA II) has been investigated by X-ray crystallography. The three dimensional atomic structure of the enzyme inhibitor complex has been refined at 1.9 A resolution. The crystallographic R-factor is 17.8%. All inhibitor atoms are clearly possible to identify from the difference electron density map in the active site of the enzyme. The nitrogen of the sulphonamide group of the inhibitor is bound as a fourth ligand to the zinc ion, the other three are all histidyl residues. The binding conformation of the sulphonamide groups is similar to the previously described sulphonamide inhibitors. One of the oxygens of the outer sulphonamido group of the inhibitor forms a hydrogen bond to the amino group of Gln 92. The higher affinity of the benzolamide inhibitor compared with acetazolamide can be accounted for by the strong aromatic and hydrophobic interactions between the amino benzene ring of the inhibitor and the residues Phe 131 and Leu 198. In modelling studies of bovine carbonic anhydrase III (BCA III) it was evident that Phe 198 prevents an optimal interaction with sulphonamides.