Pustulosis palmaris et plantaris (PPP) is known to be a one of the tonsil-related diseases because tonsillectomy is quite effective in curing this condition. However etiological association between tonsils and PPP have not fully clarified yet. Cutaneous lymphocyte-associated antigen (CLA) is known to be a specific homing receptor that facilitates T-cell migration into skin. In this study, we investigated the expression of CLA on T-cells in tonsil, peripheral blood, and skin from patients with PPP. Two-color flow cytometric and two-color immunohistological analyses revealed that the numbers of CLA/CD3 double-positive cells in freshly isolated tonsillar mononuclear cells (TMC) and in tonsillar tissues were significantly higher in patients with PPP than in patients without PPP (P<0.01, each). In vitro stimulus with alpha-streptococcal antigens enhanced CLA expression of tonsillar T-cells and TGF-beta production of TMC in patients with PPP (P<0.01, each), but did not in patients without PPP. In peripheral blood from PPP patients, the number of the CLA/CD3 double-positive cells significantly decreased at 6 months after tonsillectomy (P<0.05). The CLA/CD3 double-positive cells and the postcapillary venule that expressed with a ligand of CLA, E-selectin, were found more frequently in the plantar skin from patients with PPP as compared to that from healthy volunteers (P<0.01, each). These data suggest that a novel immune response to alpha-streptococci may enhance CLA expression on tonsillar T-cells through TGF-beta production in patients with PPP, resulting in moving of CLA-positive tonsillar T-cells to skin and tissue damages. This may play a key role in pathogenesis of PPP.