Epidemiological studies have demonstrated the effects of self-esteem on global health and life expectancy in normal aging. Endocrinological studies in humans have demonstrated the effects of self-esteem on basal regulation and reactivity of the hypothalamic-pituitary adrenal (HPA) axis. To investigate the effects of differences in self-esteem on age-related changes in cognitive performance and HPA regulation, we investigated 20 healthy elderly subjects (age range 60-84, mean age 69.8 y). We assessed salivary cortisol levels together with neuropsychological assessment, and psychological assessment for self-esteem and locus of control. Across the study sample, age was significantly associated with reductions in cognitive performance and changes in basal cortisol regulation. Self-esteem appeared independent of age. Defining two groups of subjects with high and low self-esteem, age-related changes in cognitive and endocrinological variables became more prominent in the low self-esteem group, whereas age no longer had a significant impact on the variables in the high self-esteem group. These data suggest an effect of self-esteem on cognitive decline with aging. It further suggests an effect on age-related endocrine changes in humans. These results are discussed with regard to potential mechanisms by which the reported association between self-esteem and aging could be mediated.