In the cerebrospinal fluid (CSF) of 53 patients with senile dementia of the Alzheimer type (SDAT) and 12 elderly controls, we measured somatostatin (SLI) and its molecular forms: high-molecular weight form (HMV-SST), somatostatin-14 (SST-14), somatostatin-25/28 (SST-28/25), and des-ala-somatostatin (des-ala-SST) using high pressure liquid chromatography (HPLC) and a radioimmunoassay. In SDAT, SLI was significantly decreased (p < 0.05) and correlated with dementia scores (r = -0.65, p < 0.05). HPLC separation showed a marked heterogeneity of SLI in the CSF with a preponderance of SST-14 and SST-25/28. The significant loss of SST-14 (p < 0.05) in SDAT was found to be correlated with dementia scores (r = 0.65). Moreover, qualitative and quantitative changes in the molecular pattern of SLI in SDAT indicated dysregulated synthesis and/or processing of somatostatin relating to the severity of dementia. The long-term administration of neuroleptics in severe cases of SDAT caused a significant increase of SLI (p < 0.05) and influenced the ratio of HMV-SST/SST-14 and SST25/28/SST-14.