Acetyl-L-carnitine (ALC) is a compound acting as an intracellular carrier of acetyl groups across inner mitochondrial membranes. It also appears to have neuroprotective properties and it has recently been shown to reduce attention deficits in patients with Alzheimer's disease (AD) after long-term treatment. We performed an open study to evaluate the effect of ALC (2 g/day orally for 3 months) in association with donepezil or rivastigmine in 23 patients with mild AD who had not responded to treatment with acetylcholinesterase inhibitors (AChE-I). Clinical effects were evaluated by assessing cognitive functions, functional status and behavioural symptoms. The response rate, which was 38% after AChE-I treatment, increased to 50% after the addition of ALC, indicating that the combination of these two drugs may be a useful therapeutic option in AD patients. These data do not permit a conclusion as to the possible mechanism of action of the association of the two treatments.