Mismatch negativity has been found to decline in amplitude with increasing age and also in Alzheimer's disease. It has been suggested that the reduction in amplitude of mismatch negativity in Alzheimer's disease is the result of fatigue rather than a generalized decline in neuronal response. We tested this hypothesis by measuring the effect of time on task on the visual mismatch negativity in both normal aging and in Alzheimer's disease. In older adults, visual mismatch negativity showed a reduction in amplitude, which did not vary with time on task. This argues against fatigue as the cause of visual mismatch negativity amplitude reduction in normal ageing. In Alzheimer's disease, visual mismatch negativity was virtually absent in responses to the first 16 deviant stimuli but present in response to subsequent deviants. This is opposite to the effect predicted by the fatigue hypothesis. It suggests that individuals with Alzheimer's disease are initially refractory to stimulus change.