The role of muscle cells in the survival of embryonic motoneurons projecting to the developing wing was directly examined. Embryos lacking muscle in one of their wings were produced by surgically removing the embryonic precursors of muscle cells, the somites. The resulting limb lacked only muscle cells, with the derivatives of the other limb contributor, the lateral plate mesoderm, left intact. Counts of apparently healthy lateral motor column (LMC) motoneurons supplying normal wings between stages 28 and 36 showed little decline in motoneuron number until stage 34; approximately 24% of the motoneurons died between stages 34 and 36. In contrast, the number of LMC motoneurons supplying muscleless wings declined progressively from stages 28 to 36. This decline resulted in the loss of about 77% of the motoneurons present at stage 28. In addition, the LMCs supplying muscleless wings had fewer motoneurons at all stages examined than similarly staged controls; this difference ranged from 27% in the youngest cases to 75% in the older embryos. Motoneurons were lost equivalently from all rostrocaudal levels of the brachial LMC. From these studies we conclude that motoneurons survival depends on the presence of muscle cells in the developing wing. In the absence of muscle cells, motoneuron death was increased compared to normal embryos at stages prior to the onset of naturally occurring cell death.