Rat liver oxidative stress caused by toxic hepatitis is accompanied by increased activity of glucose-6-phospate dehydrogenase (EC 1.1.1.4.9; G6PDG). Electrophoretically homogenous G6PDG preparations purified from livers control rats and animals with hepatitis had specific activity of 4.13 and 6.54 EU, respectively. Fe2+ and Cu2+ ions showed non-competetive type inhibition of G6PDG at normal and under pathological condition, whereas Ca2+ activated G6PDG. Hydrogen peroxide exhibited mixed type inhibition of G6PD (K(i) 0.36 mM and 0.95 mM at norm and experimental toxic hepatitis, respectively). The participation of oxidised and reduced glutathione in G6PDG activity regulation has been shown.