Leech sensory afferents change their growth behavior as they enter the CNS. Arriving from the periphery in fasciculated tracts, they abruptly defasciculate and expand into diffuse trees before reassembling into four distinct central tracts. In the organ-cultured germinal plate, growing sensory afferents were incubated with monovalent Fab fragments of the Lan3-2 antibody, which recognizes a 130 kd sensory neuron protein by its mannose epitope. Very low concentrations of Lan3-2 (6 and 12 nM) specifically inhibited the central defasciculation of sensory afferents, which then continued growing as a single tract. In contrast, monoclonal antibody Lan3-6, which binds to an internal sensory antigen, failed to yield the same effect. These observations suggest that this sensory neuron 130 kd surface glycoprotein participates in a developmentally significant heterophilic interaction specific for the CNS.