Peripheral nerve fibers growing from the spinal cord or dorsal root gnaglion are proposed to be under the influence of differentiating target tissues. The differentiative state of the target tissues may be critical in effecting appropriate nerve fiber pathway formation and subsequent innervation. Both peripheral limb mesenchyme and developing spinal cord, or products of them, may affect the initiation of growth, the elongation and branching of nerve fibers and their orientation. As such, the interactions of these differentiating tissues of the spinal reflex arc may explain the general means by which nerve fibers seek their targets. The results are expected to elucidate the normal control mechanisms of nerve growth during development. This investigation incorporates studies utilizing an in vitro paradigm to describe the morphogenetic relationships of central nervous system tissues, the sensory ganglia and peripheral mesenchyme and muscle. These types of relationships are suggested to be an extension of epithelial-mesenchymal interactions. A series of tissue culture experiments of various combinations of larval frog spinal cord explants, dorsal root ganglia and differentiating peripheral tissues have been undertaken with a view toward determining the influence of interacting neural and non-neural tissues on neuritic outgrowth.