The earliest known left-right asymmetric genes are expressed at Hensen's node during chick gastrulation. Gene expression following reorientation of the node shows asymmetry is instructed by adjacent tissue, hence left-right information originates outside the node. Subsequently, the node signals back to the lateral tissue, initiating a cascade leading to left-sided expression of nodal in the lateral plate mesoderm. Loss of nodal expression in the presence of blocking antibodies confirms that Sonic hedgehog is the key signal conveying left-right information from the node; however, manipulation of explant cultures suggests that the induction of nodal requires secondary signals produced in the paraxial mesoderm. These experiments establish the time of action of these signals to and from Hensen's node in establishing left-right asymmetry.