We prospectively evaluated 21 patients with prolonged ventilator dependency, to determine the frequency of unsuspected neuromuscular disease as a cause of this condition, and to determine the types of such diseases. Assessment was performed with routine and specialized electrophysiologic procedures. None of the patients had known prior neuromuscular disease, and none had ongoing medical problems that could account for their continued ventilator dependency. Sixty-two percent were found to have a neuromuscular disease severe enough to account for the ventilator dependency. Most of the remaining cases had a contributory neuromuscular disease. In addition to critical illness polyneuropathy, several other significant categories were identified. Myopathic EMG changes were found in 50% of the subgroup assessed by quantitative EMG. We conclude that neuromuscular disease is the most important factor in prolonged ventilator dependency, and that diseases other than critical illness polyneuropathy represent an important cause of this syndrome.