The investigation of interactions between growing neurites and target cells during the development of the sensible corneal innervation is of crucial importance for understanding certain corneal diseases which are related to abnormal patterns of innervation. The purpose of the present work was to establish a culture system of cornea and trigeminal neurons and to examine interactions between these tissues. The responses of neurons derived from explanted embryonic chick trigeminal ganglia to co-explanted slices prepared from embryonic cornea were monitored over several days in culture. The growth of trigeminal fibers, but not of neurites derived from control tissues such as trigeminal mesencephalic nucleus or ciliary ganglion, was preferentially directed towards the co-cultured corneal slices. The ingrowth of trigeminal axons into the cornea was followed by formation of elaborate axonal terminal branches. Individual dissociated trigeminal neurons of pseudo-unipolar or bipolar classes developed their typical morphologies in culture. In co-cultures with corneal slices, they reacted to the corneal co-explant by frequently retracting some branches and forming or elongating other ones, which were predominantly directed towards the target tissue. In addition, the presence of a co-explanted trigeminal ganglion increased the rate of growth in the dissociated trigeminal neurons. The effect was not additive when cornea was present. Antibodies against nerve growth factor (NGF) and the low-affinity p75-NGF receptor (LANGFR) revealed that trigeminal ganglion cells support neuritic growth by secreting NGF, whereas corneal cells secrete additional factor(s) which act via the LANGFR.