The directed growth of axons to their peripheral targets during development may be influenced by a variety of intrinsic and environmental factors, the latter including the pattern of extracellular matrix components in the region through which they grow. We investigated the localization within the chick trigeminal mesenchyme of a variety of extracellular matrix molecules (laminin, heparan sulfate proteoglycan, entactin, collagen type IV) by using indirect immunofluorescence techniques. The trigeminal mesenchyme contained several of these molecules, but only laminin was specifically localized to trigeminal axon pathways. Double immunofluorescence localization of affinity‐purified laminin antibodies and monoclonal antibodies directed against a neuron‐specific β‐tubulin (to visualize growing axons and postmitotic V ganglion neurons) demonstrated that the V motor and sensory peripheral nerves confine their growth to two patches of laminin‐rich mesenchyme—a ganglionic laminin patch colocalized with V ganglion neurons and their axons, and a mandibular laminin patch colocalized with the V motor axons. Thus, laminin pathways in the mesenchyme may help guide V axons along their appropriate routes in the periphery. Double immunofluorescence localization of these laminin antibodies and monoclonal antibodies that recognize neural crest cells (to visualize precursors of V ganglion neurons and glia) demonstrated that the majority of cells within the ganglionic laminin patch were neural crest and differentiating neurons derived from the trigeminal epidermal placode. Since these cells often were laminin‐immunopositive, they might be a source of the ganglionic laminin matrix. The mandibular laminin patch contains nearly no neural crest cells, and probably contains the somitomeric precursors to the mandibular muscle mass. These results suggest that laminin, a matrix molecule implicated in the guidance of trigeminal peripheral axons, might be produced in localized patches by peripheral nervous system components and by muscle targets.