The expression of GAP-43 in developing and regenerating neurons has been well characterized, but the function of this membrane-bound phosphoprotein is still unclear. Although GAP-43 is considered to be neuron-specific, it is also expressed in various glial cells of the peripheral and central nervous systems and in at least two populations of mesenchymal cells in the developing chick limb. GAP-43 mRNA is expressed transiently in developing limbs, which contain axons of spinal cord and dorsal root ganglion neurons, but do not contain neuronal cell bodies. This expression is correlated temporally with the in-growth of neurites and axons to the limbs, but appears to be independent of nerves. In some regions of the limb, GAP-43 immunoreactivity co-localizes in cells that are also immunoreactive for meromyosin, a muscle-specific marker. In addition, GAP-43 mRNA and protein are particularly abundant in the interdigital mesenchyme that undergoes apoptosis, or programmed cell death. GAP-43 has been postulated to mediate rapid changes in cell shape and the extension of processes in neuronal growth cones and elongating axons. We suggest here that GAP-43 may serve a similar function in glial cells, in myoblasts fusing to form myotubes, and in apoptotic and phagocytic cells of the interdigital mesenchyme.