In this study we investigated immune-associated antigens of peripheral lymphocytes from patients with Alzheimer's disease (AD). The patients were divided into two groups--mild and moderately severe--according to severity of disease stage, and their lymphocytes were compared to those of elderly controls. In the mild stage of the disease we observed a slight increase in the HLA-DR marker (9.5 +/- 2.4% vs 6.5 +/- 1.1%; P = 0.06), but no changes in the CD4, CD8, and interleukin-2 receptor (IL-2R) markers. In the moderately severe stage, we observed a significant increase in the HLA-DR (18.5 +/- 2.7%) and CD4 markers (55.2 +/- 3.5% vs 43.5 +/- 2.1%, P < 0.01), and a slight decrease in the CD8 subset (19.5 +/- 1.4% vs 22.3 +/- 1.3%, P = 0.05). In the same group, following stimulation with the mitogen PHA, we observed a marked reduction in IL-2R expression (30.9 +/- 4.7% vs 41.1 +/- 2.7%, P = 0.05) and in the proliferative ability of lymphocytes (21131 +/- 4676 cpm vs 47909 +/- 1107 cpm, P < 0.04). However, mitogen-induced IL-2 secretion levels from the same lymphocytes were significantly elevated (17.4 +/- 4.8 U/ml vs 8.6 +/- 4.3 U/ml, P < 0.01). Marked changes in immunological parameters in the moderately severe group support the hypothesis of a peripheral immune reaction in AD which may be correlated with the clinical stage of the disease.