Spontaneous natural killer (NK) cell activity and NK-induced cytotoxicity after interferon-gamma (IFN-gamma) were measured in healthy elderly subjects and in patients with senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID). Normal basal and IFN-gamma-stimulated NK cytotoxicity were found in healthy old subjects and in patients with MID. On the contrary higher NK cytotoxicity after IFN-gamma (650 IU) was demonstrated in SDAT patients than in MID and healthy subjects (p < 0.001). A significant inverse correlation between the percent increase of NK cytotoxicity after IFN-gamma and the Mini Mental State Examination score (p < 0.001) was also demonstrated in patients with SDAT. Our data might suggest a cytokine-dependent mechanism of NK activation in SDAT associated with the neuroimmune hypothesis of the disease.