Transforming growth factor-beta (TGF-beta) is a major modulator of the extracellular matrix and cell growth, and shows affinity for and interaction with several substances present in plaques in Alzheimer's disease (AD). In order to examine a possible role of TGF-beta in plaque biogenesis, we studied its distribution in the limbic system of AD and Down's syndrome (DS) brains. Select plaques displayed TGF-beta 1 immunoreactivity in AD and DS. TGF-beta 1 plaques were mainly located in the molecular layer of the dentate gyrus in AD, while in DS TGF-beta 1 plaques were preferentially located in the entorhinal cortex. In AD, TGF-beta 1 immunoreactivity was also shown in neurofibrillary tangles. The presence of TGF-beta 1 in plaques suggests that TGF-beta 1 may play a role in the cascade of events leading to plaque formation.