The growth-associated and presynaptic protein GAP-43 is important for axonal growth during brain development, for synaptic plasticity and in axonal regeneration [Benowitz, Routtenberg, TINS 12 (1987) 527]. It has been speculated that such growth may be mediated by cytoskeletal proteins. However, the interaction of GAP-43 with proteins of the presynaptic terminals is poorly characterized. Here, we analyze GAP-43 binding to cytoskeletal proteins by two different biochemical assays, by blot overlay and sedimentation. We find that immobilized brain spectrin (BS) is able to bind GAP-43. In contrast, little binding was observed to microtubule proteins and other elements of the cytoskeleton. Since GAP-43 is located presynaptically, it may bind to the presynaptic form of BS (SpIISigma1). It is attractive to think that such an interaction would participate in the structural plasticity observed in growth cones and adult synapses.