T cells constitute a large population of cellular infiltrate in atopic/allergic inflammation and a dysregulated, Th2‐biased peripheral immune response appears to be an important pathogenetic factor. In atopic dermatitis, circulating cutaneous lymphocyte‐associated antigen‐bearing (CLA⁺) CD45RO⁺ T cells with skin‐specific homing property represent an activated memory/effector T cell subset. They express high levels of Fas and Fas ligand and undergo activation‐induced apoptosis. The freshly purified CLA⁺ CD45RO⁺ T cells of atopic individuals display distinct features of in vivo‐triggered apoptosis such as pro‐caspase degradation and active caspase‐8 formation. In particular, the Th1 compartment of activated memory/effector T cells selectively undergoes activation‐induced cell death, skewing the immune response toward surviving Th2 cells in atopic dermatitis patients. The apoptosis of circulating memory/effector T cells was confined to atopic individuals whereas non‐atopic patients such as psoriasis, intrinsic‐type asthma, contact dermatitis, intrinsic type of atopic dermatitis, bee venom allergic patients, and healthy controls showed no evidence for enhanced T cell apoptosis in vivo. These results define a novel mechanism for peripheral Th2 response in atopic diseases. —Akdis, M., Trautmann, A., Klunker, S., Daigle, I., Küçüksezer, U. C., Deglmann, W., Disch, R., Blaser, K., Akdis, C. A. T helper (Th) 2 predominance in atopic dermatitis is due to preferential apoptosis of circulating memory/effector Th1 cells. FASEB J. 17, 1026–1035 (2003)