We examined the role of muscles in counteracting static loads in the transverse plane at the knee to determine if (a) knee muscles are activated to counteract isometric varus or valgus loads, (b) muscle activity during varus and valgus loads changes with the angle of knee flexion, and (c) the direction of a muscle's activation can be predicted by its moment arm orientations. For seven subjects, muscle activity was recorded during isometric tasks using surface and intramuscular electrodes from 10 muscles that span the knee. A six-degree-of-freedom load cell was rigidly attached to each subject's lower leg just above the ankle, and the subjects were instructed to push against the load cell so as to produce moments in the flexion-extension-varus-valgus plane at the knee. Moments in this plane were all of equal magnitude and varied in direction the full 360 degrees in 20 degrees increments. Most muscles were not activated to stabilize the knee against varus-valgus loads, but the sartorius, gracilis, and tensor fasciae latae showed substantial electromyographic activation in these directions. The load directions where muscles were principally active were observed to be dependent on joint angle for some muscles. In particular, the principal directions of activation for these three muscles changed as the angle of knee flexion changed. Similarly, a muscle's moment arm orientation was a good predictor of direction of activation for some muscles and a poor one for others. These results suggest that different muscles may play different roles in providing joint stability and that these roles are complex functions of muscle moment arm orientations, joint angles, external load directions, and possibly other undetermined parameters.