ABSTRACT Migrating embryonic growth cones require multiple, membrane-associated signalling molecules to monitor and respond to guidance cues. Here we present the first evidence that vertebrate cell adhesion molecule-like protein tyrosine phosphatases are likely to be components of this signalling system. CRYPα, the gene for an avian cell adhesion molecule-like phosphatase, is strongly expressed in the embryonic nervous system. In this study we have immunolocalised the protein in the early chick embryo and demonstrated its predominant localisation in axons of the central and peripheral nervous systems. This location suggests that the major, early role of the enzyme is in axonal development. In a study of sensory neurites in culture, we furthermore show that this phosphatase localises in migrating growth cones, within both the lamellipodia and filopodia. The dependence of growth cone migration on both cell adhesion and signalling through phosphotyrosine turnover, places the cell adhesion molecule-like CRYPα phosphatase in a position to be a regulator of these processes.