The trigeminal region of the chick was studied with indirect immunofluorescence in order to determine whether extracellular matrix components might be distributed in such a way as to guide trigeminal axons to their peripheral targets in the mandibular arch. Tissue sections from stages 13–15 and 21/22 were immunolabeled indirectly with affinity-purified antibodies raised against fibronectin and laminin, two extracellular matrix glycoproteins that support axon growth in vitro. Fibronectin was distributed ubiquitously throughout the head mesenchyme prior to and during initial axon growth from the brainstem (stages 13–15). Shortly after trigeminal axons reached their target tissues (stage 21/22), fibronectin immunolabeling was distributed throughout the head mesenchyme, but was present only at low levels in the trigeminal ganglion and motor nerve. Laminin immunolabeling was distributed in the lateral head mesenchyme at stage 13 as small specks and patches. At stage 14, when the motor axons first exit from the brainstem, short, linear arrays of laminin immunostaining were present from the basement membrane of the neural tube to the core of the mandibular arch, and many were parallel to the direction of axon growth. By stage 21/22 the trigeminal ganglion and motor root showed intense antilaminin immunofluorescence as did the central core of the mandibular arch. These studies suggest that the distribution of fibronectin within the head mesenchyme cannot give directional information to the growing trigeminal axons because of its homogeneous distribution. However, the initial distribution of laminin during the earliest stages of axon outgrowth may provide an extracellular matrix pathway that permits trigeminal axons to reach their targets.