Alopecia areata (AA) is a putative autoimmune disease of the skin with an inflammatory component that can be treated by the local application of contact sensitizers. Here, we explored whether responsiveness toward diphenylcyclopropenone (DPCP) is reflected by the composition and the activation state of peripheral blood mononuclear cells (PBMCs). PBMCs of 43 AA patients, 26 treated and 17 untreated, and of 31 healthy volunteers were tested. AA patients' PBMCs differed from that of healthy donors by a slight increase in CD16- and tumor necrosis factor-α (TNF-α)-expressing cells. These features were independent of the disease state and treatment. Additional changes in the activation state of PBMCs, upregulation of the costimulatory molecules CD40 and CD80, of the accessory molecule CD154, and of interferon-γ expression were identified only in AA patients where the disease was advancing, i.e. these changes were independent of the extent of hair loss and were not seen in patients with spontaneous or DPCP treatment-induced, regressing AA. Thus, the progressive state of AA is accompanied by a systemic activation of T cells, and the therapeutic efficacy of treatment can be estimated by restoration of the non-activated state. Furthermore, an increase in CD16+- and TNF-α-expressing cells may contribute to AA susceptibility.