Alzheimer''s disease (AD) and frontotemporal dementia (FTD) are the most common types of progressive neurodegenerative disorder in our catchment area. The distribution of cortical degeneration in FTD is mainly the reverse of that in AD, while there are both differences and similarities in the clinical characteristics. Somatostatin and neuropeptide Y (NPY) are neuropeptides with a widespread distribution in the human cerebral cortex. Somatostatin is involved in the regulation of hormone release from the anterior pituitary and may act as a neurotransmitter-modulator. NPY is a potent anxiolytic neuropeptide. Somatostatin and NPY coexist in the cerebral cortex, basal ganglia and in amygdaloid complexes. The present study of AD (n = 34) and FTD n = 22) analyses the cerebrospinal-fluid (CSF) levels of somatostatin-like immunoreactivity and NPY-like immunoreactivity and correlates their levels to 54 different clinical items, such as restlessness, anxiety, irritability and depression. The CSF levels of the two neuropeptides somatostatin and NPY were significantly correlated in FTD (p < 0.02), but not in AD. Several significant correlations to the clinical signs were found: in AD disorientation and dyspraxia, and in FTD agitation, irritability and restlessness. Somatostatin showed a significant negative correlation with severity of dementia in AD (p < 0.013).