A series of 8 enzymatic reactions are responsible for the conversion of ATP and PRPP to histidine. Curiously, two of the reactions, which are non-sequential, are carried out by the same protein. Is this mere happenstance or a suggestion that all of the proteins in this series interact to form a complex? Although sucrose gradient centrifugation was developed precisely to ask this question, the negative result may merely have reflected the enormous dilution involved in these assays. New techniques of molecular crowding and cooperative enzyme kinetics will be employed to readdress this question.