A point mutation in the structural gene for purine hydroxylase I (xanthine dehydrogenase) of Aspergillus nidulans results in several dramatic pleiotropic effects. The mutant enzyme oxidises 2-hydroxypurine at position 6 rather than 8, shows a 70-fold reduction in the V for hypoxanthine, and loses the ability to accept xanthine as a substrate. Allopurinol, a powerful pseudoirreversible inhibitor of the wild type enzyme, behaves as a good substrate of the mutant enzyme. We propose that the substrate and inhibitor specificities of the enzymes depend on the relative position of an orientating site ann a catalytic site. All the properties of the mutant enzyme can be explained by assuming that the mutation results in a change of the relative positions of the catalytic and orientating sites. We have assumed that the catalytic site comprises a Mo(VI) atom and an--S-group as proposed by Coughlan [FEBS Lett. 81, 1--9 (1977)] and the orientating site is a lysyl residue. While these assumptions are not strictly necessary for the construction of an abstract geometric model, they are consistent with other data bearing on the structure of the active site of the molybdenum-containing hydroxylases.