We studied the effect of tetrahydroaminoacridine (THA) on cerebrospinal fluid somatostatin-like immunoreactivity (CSF-SLI) in probable Alzheimer disease (AD) patients (n = 20) who took part in an open THA treatment trial. The maintenance dose (100 mg/day) was continued for 4 weeks. Samples of CSF were obtained before treatment and at the end of the treatment period. The CSF-SLI increased significantly (P = 0.01) in the responders for the treatment (increase of the Mini-Mental State Examination score greater than or equal to 3; n = 11), while the non-responders (n = 9) showed a significant decrease of CSF-SLI (P = 0.003). The change of CSF-SLI had also a significant correlation (P = 0.001) with neuropsychological performance. We conclude that the effects of of THA on the CSF-SLI may be due to presynaptic cholinergic or direct somatostatinergic stimulation.