We used intact fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles from rats and mice to test the hypothesis that exogenous application of an oxidant would increase maximum isometric force production (P(o)) of slow-twitch muscles to a greater extent than fast-twitch skeletal muscles. Exposure to an oxidant, hydrogen peroxide (H(2)O(2); 100 microM to 5 mM, 30 min), affected P(o) of rat muscles in a time- and dose-dependent manner. P(o) of rat soleus muscles was increased by 8 +/- 1 (SE) and 14 +/- 1% (P < 0.01) after incubation with 1 and 5 mM H(2)O(2), respectively, whereas in mouse soleus muscles P(o) was only increased after incubation with 500 microM H(2)O(2). P(o) of rat EDL muscles was affected by H(2)O(2) biphasically; initially there was a small increase (3 +/- 1%), but then P(o) diminished significantly after 30 min of treatment. In contrast, all concentrations of H(2)O(2) tested decreased P(o) of mouse EDL muscles. A reductant, dithiothreitol (DTT; rat = 10 mM, mouse = 1 mM), was added to quench H(2)O(2), and it reversed the potentiation in P(o) in rat soleus but not in rat EDL muscles or in any H(2)O(2)-treated mouse muscles. After prolonged equilibration (30 min) with 5 mM H(2)O(2) without prior activation, P(o) was potentiated in rat soleus but not EDL muscles, demonstrating that the effect of oxidation in the soleus muscles was also dependent on the activation history of the muscle. The results of these experiments demonstrate that P(o) of both slow- and fast-twitch muscles from rats and mice is modified by redox modulation, indicating that maximum P(o) of mammalian skeletal muscles is dependent on oxidation.