Dominant mutations of human Cu/Zn superoxide dismutase (SOD1) are found in about 20% of patients with familial amyotrophic lateral sclerosis (FALS). A transgenic mouse model of FALS (FALSG93A mice) has been generated by overexpression of a mutated form of SOD1. Using electromyography we first show that FALSG93A mice suffer from motoneurone dysfunction similar to that observed in ALS patients and fulfill Lambert's criteria for ALS. We also showed that FALSG93A mice demonstrate a massive loss of functional motor units starting at 47 days of age. Impairment of motor neurone function preceeds by 6 weeks the onset of apparent clinical signs (shaking, tremor) and the beginning of motor neurone loss. Neuromuscular deficits in FALS mice do not result from motoneuronal cell death but rather from loss of axonal integrity.