Previous studies have suggested that estrogen may have an effect on cognitive and emotional function in women. Studies in rodents and non-human primates have demonstrated the presence of estrogen receptors in brain, and that estrogen can affect behavior in animals. Estrogen administration to ovariectomized rats increases choline acetyltransferase activity in certain regions of brain. Choline acetyltransferase activity is known to be significantly decreased in senile dementia-Alzheimer's type (SDAT). Based on these observations, we treated seven women with SDAT with low dosages of estradiol over a six week period. A battery of assessments was performed throughout the study period. Significant improvements in three women were noted on measures of attention, orientation, mood and social interaction. These estrogen-responsive women were characterized by dementia associated with an affective disorder, older age at onset, and evidence of osteoporosis. Side effects of estradiol therapy included withdrawal bleeding in one woman and transient breast tenderness in another. Estradiol therapy thus may benefit some postmenopausal women with SDAT. The occurrence of osteoporosis in the estrogen-responsive group suggests that SDAT in some women may be associated with or related to a systemic estrogen deficiency state. However, considering the potential for serious side effects as a result of estrogen therapy, the current risk to benefit ratio precludes the routine clinical use of estrogen for dementia until careful clinical research trials have been performed.