In a preliminary study of 8 patients with probable Alzheimer''s disease (AD), the effect of phosphatidyl-serine (PS; 500 mg daily for 3 weeks) on brain glucose metabolism was studied using positron emission tomography (PET) of fluor-18-deoxyglucose. In all cases, pretreatment PET studies showed the metabolic pattern typical for AD, with predominant decreases in the parieto-occipito-temporal and frontal association cortex and less involvement of primary cortical areas and subcortical structures. Global metabolic rate increased by 14.8% following treatment. A repeated-measures ANOVA demonstrated significant increases (p < 0.01) of glucose metabolism in defined cortical and subcortical structures ranging up to 20.3% in basal ganglia/thalamus and 19.3% in visual cortex. Metabolism was also increased in areas most involved in AD (13.5–16%). Independent from these regional differences, an inverse correlation was observed between metabolic values and changes during the treatment period. A significant change of MMS scores or daily life activity, however, could not be observed during the 3 weeks of treatment. This shown metabolic effect of PS encourages long-term clinical trials on larger patient populations in which the effect of an increment of glucose metabolism on cognitive, neuropsychological and daily life performance can be additionally evaluated.