The effect of tetrahydroaminoacridine (THA) on the cerebrospinal fluid (CSF) monoamine metabolites was studied in 22 patients with Alzheimer's disease in an open treatment trial. The CSF monoamine metabolites were assayed at baseline and after 4 weeks' active THA treatment with 100 mg/d. A statistically significant increase in the CSF homovanillic acid (HVA) and in 5-hydroxyindoleacetic acid (5-HIAA) content was found. The increase of the CSF 5-HIAA level correlated significantly with improvement in cognitive tests and in the Instrumental Activities of Daily Living Scale. We conclude that besides its anticholinesterase activity THA enhances also the monoaminergic neurotransmission in the brain and that the clinical improvement during THA treatment may be partly mediated through the monoaminergic system.