In the two cases reported here, acute respiratory failure developed as a manifestation of motor neuron disease (amyotrophic lateral sclerosis). Both patients complained of systemic weakness before respiratory failure occurred. In one patient, respiratory support could not be discontinued because of poor inspiratory and expiratory pressure. Although acute respiratory failure is an uncommon manifestation of motor neuron disease, we believe this disorder should be considered in patients with unexplained respiratory failure and in those who cannot be weaned from a respirator for mechanical reasons.