We have shown recently that cocultures of muscle cells from infantile spinal muscular atrophy (SMA) patients innervated by motoneurons of normal rat spinal cord explants undergo a degeneration process, suggesting that muscle may play a role in this atrophy, which previously has been considered to be a pure motoneuron disease. Conditional media of SMA cocultures did not affect control healthy nerve muscle cocultures. Conversely, conditioned media of control cocultures were unable to prevent degeneration of SMA cocultures. Moreover, neurotrophic factors, thought to be of help in motoneuron disease treatment, did not protect SMA cocultures from premature death. Our results suggest that the abnormal phenotype observed in nerve‐muscle coculture (1) is not due to the release of a toxic factor nor to the lack of a secreted survival factor; and (2) does not respond to neurotrophin treatment. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 953–960, 1997