OBJECTIVE To determine whether muscle function is compromised in healthy smokers in comparison with activity-matched non-smokers. METHODS Nine male smokers (aged 22.2 +/- 2.5 years: mean +/- SD) with a smoking history of 2.5 +/- 3.1 pack years, and ten male control participants (25.4 +/- 2.9 years) matched for physical activity level participated in this study. Knee extensor strength was measured using isometric maximal voluntary contractions. Voluntary activation of the quadriceps and co-activation of the biceps femoris were determined using interpolated twitches and surface electromyography respectively. The frequency-torque relationship and fatigue resistance were assessed with electrically evoked contractions. A fatigue index was determined as the ratio of final torque to initial torque during a series of isometric contractions (2 min; 30 Hz; 1 s contraction/1 s rest). Quadriceps anatomical cross sectional area was measured with MRI at 50% of femur length. RESULTS Maximal voluntary contraction torque, quadriceps anatomical cross sectional area, knee extensor torque/quadriceps cross sectional area, activation, co-activation and force-frequency relationship were similar, whereas the fatigue index was 17% lower in smokers than non-smokers. CONCLUSIONS In young men smoking does not significantly affect quadriceps muscle mass and contractile properties, but does reduce fatigue resistance of the quadriceps muscle, which was not attributable to differences in physical activity.