The fastest, most forceful motor units are lost progressively during asymptomatic disease in the SOD1(G93A) transgenic mouse model of amyotrophic lateral sclerosis. As the disease progresses the surviving motor units must increase their levels of activity to sustain posture and movement. If activity-dependent conversion of motor units to more fatigue resistant types increased their resilience and hence survival, we hypothesized that an experimental increase in motor unit activity in the hindlimb muscles of the SOD1(G93A) transgenic mouse should "save" those motor units that are normally lost in the first 90 days of age. To test this hypothesis, we partially denervated hindlimb muscles in SOD1(G93A) and their corresponding control SOD1(WT) transgenic mice by avulsion of either L4 or L5 spinal roots at 40 days of age. Whole muscle and single motor unit isometric twitch forces were recorded and the numbers intact motor units in fast-twitch tibialis anterior, medial gastrocnemius, extensor digitorum longus muscles and the slow-twitch soleus muscle were calculated at 90 days of age. We found that the rapid age-dependent decline in numbers of functional motor units in fast-twitch muscles of the SOD1(G93A) transgenic mice was dramatically reduced by the functional hyperactivity in the partially denervated muscles and, that these muscles comprised a significantly higher component of type IIA and type IID/X fibers than those muscles that were innervated by nerves in intact spinal roots. We conclude that the vulnerable motor units are saved by increasing their neuromuscular activity and consequently, converting them to slower, less forceful, fatigue resistant motor units.