A study has been made of the effects of Schwann cells isolated from neonatal sciatic nerve on motoneurones in culture. Motoneurones were identified in dissociated spinal cord cultures from 6-day avian embryos by prior retrograde labelling with rhodamine-latex microspheres. Schwann cells trebled the expression of long neurites in these motoneurones over that in control media as well as maintaining them viable for 24 h. A transformed Schwann cell line, RN22, produced similar results. These effects were mediated by a soluble factor(s) released from the Schwann cells which was distinct from nerve growth factor. Schwann cells exerted this initiation of neurites on homogeneous cultures of motoneurones, indicating that other spinal cord cells are not necessary to mediate this effect. The observations are discussed in terms of the hypothesis that Schwann cells guide motor axons during regeneration and formation of limb and muscle nerves.