Accumulating evidence suggests that testosterone has neurotrophic and perhaps neuroprotective actions. Thus, age-related depletion of testosterone may increase the brain's vulnerability to Alzheimer's disease and related disorders. To begin investigating this issue, cultured neurons were exposed to the Alzheimer-related insult beta-amyloid in the presence of testosterone. beta-Amyloid neurotoxicity was significantly reduced by testosterone via a rapid, estrogen-independent mechanism. These data may provide additional insight into the treatment of age-related neurodegenerative disorders.