A striking feature of the outgrowth of motor axons from the embryonic chick spinal cord is the accuracy with which they grow to correct target muscles in the limb. Studies involving the surgical manipulation of the early neural tube or limb bud have led to the conclusion that motoneurons are specified or acquire distinctive properties early in development that enable them to detect and respond to specific cues in the periphery. We have recently carried out studies to identify the cells or tissues responsible for producing these cues. Major contributors to the outgrowing axon's environment are the lumbosacral (LS) somites which give rise to limb muscle cells and the LS somatopleural mesoderm which gives rise to limb connective tissues. To determine whether the LS somites contain specific guidance information at stages when motoneurons are known to be specified, motor projections were assessed in chick embryos after early somitic tissue reversals. The finding of normal projection patterns suggests that the LS somites do not contain such information at early stages. To assess the role of the LS somatopleural mesoderm in specific axon guidance, we examined motor projections in embryos where the LS somatopleural mesoderm had been shifted anteriorly before limb bud formation. In these embryos the limb developed in an anteriorly shifted position. LS motoneuron axons entered the posterior part of the limb but then extended anteriorly along aberrant paths to innervate appropriate muscles. These observations suggest that it is the precursor of limb connective tissues that is the source of specific axon guidance cues.