Work on nerve growth factor has established that the survival of developing vertebrate neurones depends on the supply of a neurotrophic factor from their target field. The discovery of several new neurotrophic factors has raised the possibility that neurones which innervate multiple target fields require several different neurotrophic factors for survival. Here we show that two distinct neurotrophic factors, one in the central nervous system (CNS) and the other in skeletal muscle, promote the survival of proprioceptive neurones in culture. At saturating concentrations, either factor alone supported most neurones and there was no additional survival in the presence of both factors, but at subsaturating concentrations the combined effect was additive. The neurotrophic activity of each factor was greatest during the period of natural neuronal death. Our results demonstrate that each cultured proprioceptive neurone responds to two distinct neurotrophic factors present in its respective central and peripheral target fields, and suggest that these factors cooperate in regulating survival during development.