Human muscles paralyzed chronically by spinal cord injury (SCI) fatigue excessively. Whether these reductions in force reflect a decrease in the fatigue resistance of the motor units is unknown. Our aim was to determine the fatigability of thenar motor units paralyzed chronically (10 ± 2 years) by cervical SCI. Surface electromyographic activity (EMG) and force were recorded from 17 paralyzed motor units (n=7 subjects) in response to intraneural motor axon stimulation (13 pulses at 40 Hz, 1/s for 2 min). Unit force decreased progressively, reaching 8-60 % of initial after 2 min, whereas both the amplitude and area of the first EMG potentials in the trains increased significantly (both P < 0.05). Thus, transmission of neural signals to the sarcolemma was effective and the reduction in force must reflect impaired processes in the muscle fibers. The median fatigue index for paralyzed units (0.31), the ratio of the force at 2 min compared to the initial force, was significantly lower than that for units from control subjects (0.85, P < 0.05), but the distribution of fatigue indices for each population had a similar shape (ranges: 0.08-0.60 and 0.41-0.95, respectively). Hence, chronic paralysis did not limit the range of fatigability typically found for thenar units, only its magnitude. These findings suggest that all paralyzed units underwent similar reductions in fatigue resistance. After fatigue, paralyzed unit forces were reduced at all frequencies (1-100 Hz, P < 0.05). Twitch contraction and half-relaxation times were increased, as was the frequency needed to produce half maximal force (P < 0.05). Thus, stimulation protocols used to produce functional movements in paralyzed muscles need to accommodate the significant and rapid fatigue of the motor units.