To date, the neurotrophic factor requirements of developing sensory neurons have been studied using heterogeneous populations of neurons that innervate a wide variety of different sensory structures. To ascertain the particular neurotrophic factor requirements of different kinds of sensory neurons and to determine whether these requirements are related to the type of sensory receptors innervated, it is necessary to study homogeneous preparations of functionally distinct sensory neurons. For this reason I have studied the influence of a soluble extract of skeletal muscle on the survival and growth of proprioceptive neurons isolated from the trigeminal mesencephalic nucleus (TMN) of the embryonic chick. Explants of the TMN and dissociated glia-free cultures of TMN neurons were established from chick embryos of 10 to 18 days incubation (E10 to E18). Skeletal muscle extract prepared from E18 chick pectoral muscle and enriched for neurotrophic activity by ammonium sulfate fractionation promoted marked neurite outgrowth from explants and substantial survival in dissociated cultures established during the period of natural neuronal death in the TMN. In these latter cultures 70 to 80% of the neurons survived and grew in the presence of the extract compared with less than 2% in control cultures. At later ages, following the period of natural neuronal death, these effects were less marked. The neurotrophic activity of extracts prepared from muscle of different ages increased steadily from E10 to E20 (the oldest muscle studied). The active factor is heat labile, trypsin sensitive, and non-dialyzable, it is neither functionally nor immunochemically related to NGF and it has negligible neurotrophic effect on the predominantly cutaneous sensory neuron population of the trigeminal ganglion. These findings demonstrate that skeletal muscle contains a neurotrophic factor which supports the survival and growth of proprioceptive neurons and suggest that this factor has some specificity among functionally distinct kinds of sensory neurons.