Previous work on the coordination between the upper and lower limbs has invariably shown that its accuracy/stability is primarily determined by the mutual direction between limbs in extrinsic space and not by muscle relationships. Here we show that muscle grouping does play a critical role in coordination of the arm and leg, in addition to direction. More specifically, the simultaneous activation of isofunctional muscles and/or limb movements proceeding in the same direction, results in more successful performance than the alternated activation of isofunctional muscles and/or movements occurring in different directions. In the absence of isofunctional muscle coupling, the mutual direction between the limbs plays a more prominent role in determining coordinative accuracy. These coordination constraints can largely account for the observed differences between ipsilateral and heterolateral limb coordination. The findings are discussed in view of the coalition of coordination constraints.