Graft‐versus‐host disease (GvHD) is a serious complication of allogeneic stem cell transplantation (SCT) affecting the skin, gut and liver. The involvement of distinct organs suggests a role for tissue‐specific chemokines and their receptors in directing activated donor T cells to these sites. In this study the potential involvement of the skin‐specific CCL27/CTACK‐CCR10 interaction was investigated in 15 paediatric SCT patients with skin GvHD. During the course of skin GvHD, peripheral blood T cells from these patients contained a high proportion of CD4⁺ CCR10⁺ T cells that disappeared after the GvHD was resolved. These cells were CD45RO⁺, expressed additional skin homing markers (cutaneous lymphocyte‐associated antigen and CCR4), and produced the T‐cell helper type 1‐cytokines tumour necrosis factor‐alpha and interleukin‐2. The increase in CD4⁺ CCR10⁺ T cells was absent in SCT patients without GvHD. Immunohistochemical investigations showed CD4⁺ CCR10⁺ T cells in the GvHD skin biopsies of the same patients, but not in the gut biopsies of patients also suffering from gut GvHD. The infiltration of CD4⁺ CCR10⁺ T cells in the GvHD‐affected skin correlated with an enhanced epidermal expression of CCL27/CTACK, the ligand for CCR10. These findings support the involvement of CCL27/CTACK‐CCR10 interaction in recruiting CD4⁺ T cells to the skin, thus contributing to the pathogenesis of acute GvHD.