In vertebrates, commissural axons pioneer a clrcumferentlal pathway to the floor plate at the ventral midline of the embryonic spinal cord. Floor plate cells secrete a diffusible factor that promotes the outgrowth of commlssural axons In vitro. We have purified from embryonic chick braln two protelns, netrin-1 and netrln-2, that each possess commissural axon outgrowth-promoting actlvlty, and we have also identlfied a distinct activity that potentiates their effects. Cloning of cDNAsencoding the two netrins shows that they are homologous to UNC-6, a laminln-related protein required for the circumferential migration of cells and axons in C. elegans. This homology suggests that growth cones In the vertebrate spinal cord and the nematode are responsive to similar molecular cues.