We investigated whether the lower fatigue resistance in smokers than in nonsmokers is caused by a compromised muscle oxidative metabolism. Using calibrated histochemistry, we found no differences in succinate dehydrogenase (SDH) activity, myoglobin concentration, or capillarization in sections of the vastus lateralis muscle between smokers and nonsmokers. The relationship between fatigue resistance and SDH activity in nonsmokers (r = 0.93; p = 0.02) is absent in smokers. This indicates that the lower muscle fatigue resistance of smokers can likely be attributed to causes other than differences in oxidative metabolism and capillarization. © 2008 NRC.