Cyclin-dependent kinase 5 (Cdk5) and its neuron-specific regulator p35 (refs 1-4) are essential for neuronal migration and for the laminar configuration of the cerebral cortex(5-7). In addition, p35/ Cdk5 kinase concentrates at the leading edges of axonal growth cones and regulates neurite outgrowth in cortical neurons in cultures. The Rho family of small GTPases is implicated in a range of cellular functions, including cell migration and neurite outgrowth(9-13). Here we show that the p35/Cdk5 kinase co-localizes with Raf in neuronal growth cones, Furthermore, p35 associates; : directly with Rac in a GTP-dependent manner. Another Rac effector, Pak1 kinase(14,15), is also present in the Rac-p35/Cdk5 complexes and co-localizes with p35/Cdk5 and Rac at neuronal peripheries. The active p35/Cdk5 kinase causes Pak1 hyperphosphorylation in a Rac-dependent manner, which results in downregulation of Pak1 kinase activity. Because the Rho family of GTPases and the Pak kinases are implicated in actin polymerization(16-18), the modification of Pak1, imposed by the p35/Cdk5 kinase, is likely to have an impact on the dynamics of the reorganization of the actin cytoskeleton in neurons, thus promoting neuronal migration and neurite outgrowth.