The stability of the enzyme glucose dehydrogenase (GDH) has been studied under turnover conditions in an electrochemical reactor with NAD(P)(+) regeneration on a preparative scale. The enzyme showed first-order deactivation patterns closely related to imposed potential. An increase in the applied potential caused a decrease of the half-life deactivation time of the enzyme (t(1/2)). However, this detrimental effect was compensated with an enhancement of the substrate consumption rate (r(s)) attained as a consequence of the higher cofactor regeneration rates observed at more positive potentials. A 0.7 V potential (vs AgAgCl) was selected as a compromise between the activity and the stability of the enzyme (t(1/2) = 4.2 h; r(s) = 32 mu mol min(-1)). The protective effect on the activity of glucose dehydrogenase of well-known stabilizing agents such as NaCl, sorbitol, bovine serum albumin (BSA) or polyethyleneimine (PEI) has been studied. PEI(50 000 MW) at concentrations between 0.3 and 0.5 mM showed the highest protection of the enzyme activity in the electrochemical reactor as well as the highest substrate consumption rates (t(1/2) 24.5 h; r(s) = 59 mu mol min(-1)). This beneficial effect of PEI is explained in terms of an electrode, cofactor, and enzyme modification that induces an increase of the concentrations of NAD(P)H and glucose dehydrogenase in the vicinity of the electrode and minimizes the adsorption of the enzyme on the electrode contact.