Calbindin D-28K and NADPH-diaphorase have been proved to be excellent neurochemical markers for interneurons in the central nervous system and their involvement in Alzheimer's Disease (AD) has been suggested. In this study Calbindin D-28K immunoreactivity and NADPH-diaphorase enzyme histochemistry are investigated in the superior frontal and superior temporal cortex in 5 AD and 6 control brains. We found that Calbindin D-28K positive neurons are decreased in number in the cortex compared to control brains. Moreover Calbindin D-28K immunoreactive cells in AD brains exhibit neuritic degeneration. Our data support the hypothesis that a failure of calcium buffering or homeostasis may contribute to cell death. Despite slight morphological changes in the cortex, no significant difference in the number of NADPH-d/NOS positive neurons in the cortex of control and AD cases was found. NADPH-diaphorase activity seems to be relatively stable in the neurons in AD. These results provide further evidence of a selective preservation of NAPPH-d/NOS neurons in AD.