We have analysed how the behaviour of a voluntarily activated motor unit changes when subjected to 100-150 threshold cortical stimuli using peristimulus time histograms (PSTHs). This is a measure of the integrity of the corticomotoneuronal core innervating a single anterior horn cell. One hundred and thirty units in 29 patients with ALS and 35 units in eight age-matched normal controls were studied. PSTHs were constructed using 1-ms bins of stimulus triggered sweeps with a total analysis time of 250 ms (50 ms before and 200 ms after the stimulus). In ALS the primary peak of the PSTH was delayed in onset and prolonged in duration. The primary peak was further analysed by finer 0.2-ms bins, which showed in ALS there were more sub-components than normally occur. Additional sub-components in the PSTH primary peak implies a hyper-excitable corticomotoneuron that fires excessively. Excitability could be glutamate induced and/or due to failure of GABA inhibitory mechanisms. Some glutamate antagonsits may be therapeutic in ALS because of their anticonvulsant or GABergic properties rather than their anti-glutamate properties. GABA(B) agonists might have a role in future therapeutic combined therapies for ALS.