Cortisol levels in patients with Alzheimer's disease (AD) are relatively unaffected by a challenge with dexamethasone (DEX) in vivo. The present study demonstrates that DEX is less inhibitory for phytohemagglutinin (PHA)-induced T cell proliferation in AD patients as compared to age-matched controls. Since no significant differences were found between AD patients and age-matched controls with regard to the fraction of CD45RA+ or CD45RO+ CD4+ T cells nor the ability of peripheral blood mononuclear cells to produce IL-2 or IL-4, it is unlikely that the difference in DEX sensitivity is due to a changed lymphokine profile or a changed composition of the CD4+ T cell population. Sensitivity to DEX was negatively correlated with the ability to produce IL-2 and IL-4 in the controls but not in AD patients. This suggests that IL-2 and IL-4 synthesis in AD patients is less sensitive to regulation by glucocorticoids.