Oligomeric glutamic dehydrogenase from bovine liver is dissociated to inactive monomers (M r = 56 000) under a wide variety of conditions: 3 ≥ pH ≥ 12, 6 ᴍ guanidine · HCl, 6 ᴍ urea, 0.2% sodium dodecylsulfate. High hydrostatic pressure (< 1 kbar) only affects the association equilibrium of the native hexamer to higher polymers. The respective reaction volume (ΔV=28 ± 5 ml · mol -1 at 298 K, 1 bar) is linearly dependent on temperature and pressure. At p > 1.5 kbar dissociation of the hexamer occurs; this reaction is accompanied by irreversible deactivation. Depending on the denaturant applied for the monomerization, the final conformational stale of the polypeptide chain differs widely regarding its residual structure. As taken from laser light scattering measurements the rate of dissociation at pH 1.8 follows first order kinetics with a rate constant k 1 = 0.42 ± 0.06 s -1 . In the range of the oligomer ⇌ monomer transition, dissociation is accompanied by irreversible aggregation leading to inactive high molecular weight material. At low concentration (c < 5 µg/ml) this side reaction can be slowed down, so that the reconstitution of the enzyme can be monitored using spectroscopic techniques. Concentration dependent stopped-flow experiments prove the regain of fluorescence to be a rapid first order process; the respective half-times at pH 7.4 are τ 1/2 = 2.0 ± 0.5 ms and 0.7 ± 0.2 ms for the “renaturation” from 6 ᴍ guanidine · HCl, pH 6, and pH ~ 2, respectively. The product of reconstitution shows the fluorescence and circular dichroism pattern characteristic for the native enzyme. However, no reactivation can be achieved under any of the following conditions: optimum protection against chemical modification; variation of enzyme concentration, temperature, and hydrostatic pressure; addition of specific ligands such as coenzymes, substrates, ADP, membrane constituents (cardiolipin, electron transfer particles ETPH). Obviously, the “renaturation” (D → N) of glutamic dehydrogenase is governed by a side reaction according to N → D ⇌ R → A which causes aggregation of intermediates R instead of reconstitution of the native enzyme.