Although the glyoxalase system was discovered in 1913, its function in the biological network is still a subject of debate. An attractive theory on its role was described by Albert Szent-Gyorgyi in the 1960s. From a bird's eye view, the promine/retine concept of Szent-Gyorgyi seems to give a plausible role for this ubiquitous enzyme system, but on going into detail, it obviously suffers from several uncertainties which have not been discussed until now. Here, a critical overview of the theory is presented by taking the pros and cons into account. It looks as though more data object to the theory than give support to it; and the search for anticancer medicines stimulated by the theory has not resulted in a new way of treatment of tumors, either. Hence, it is feared that the theory suggested for the biological role of glyoxalase pathway cannot be accepted, as it is. (C) 1999 Elsevier Science B.V. All rights reserved.