Ten resistance trained (RT) and 6 non-resistance trained (NRT) subjects were used to determine differences in quadriceps activation between isometric single and double knee extensions and squat contractions. Greater inactivation, as measured by the interpolated twitch technique, was recorded with single (RT: 16.5%, NRT: 17.6%) than double leg extensions (RT: 8.4%, NRT: 13.4%) or squats (RT: 4.03%, NRT: 1.7%). There was no significant difference between the maximum voluntary contraction (MVC) force of the dominant leg during single and double leg extensions. However, in NRT subjects, the contralateral or non-dominant leg during double leg extensions exhibited significantly less force than the dominant leg (715.9 vs 566.9 N). This deficit may be due to a lesser reliance on the non-dominant limb. The contractions of multiple lower body muscle groups enhanced the activation of the dominant quadriceps. Greater levels of activation may be necessary to cope with the stabilization necessary for bilateral and multi-articular contractions.