Cell contact-dependent neurite outgrowth stimulated by CAMS requiresactivation of a second messenger pathway that requires the function of a tyrosine kinase upstream from calcium influx into neurons. In the present study, we present evidence that implicates activation of the fibroblast growth factor receptor (FCFR) in the pathway underlying neuriteoutgrowth stimulated by 11, N-CAM, and N-cadherin. We have identified a CAM homology domain in the FCF family of receptors and show that antibodies which bind to this domain specifically inhibit neurite outgrowth stimulated by the above CAMS. We also show that synthetic peptides derived from this domain can differentially and specifically inhibit neurite outgrowth stimulated by 11, N-CAM, and N-cadherin. In addition, a soluble Ll-Fc chimera is shown to stimulate an increase in phosphotyrosine on the same set of neuronal proteins that are phosphorylated following activation of the FGFR with basic FGF.