AbstractIn humans and rodents a population of naturally occurring CD4+CD25+ T cells are suppressor T (CD25+ Ts) cells, which are considered to maintain peripheral immunological tolerance. Recently, we have described a unique chemotactic response profile for human CD25+ Ts cells, but their homing potential remains poorly defined. Here, we document a heterogeneous homing potential of human peripheral blood CD25+ Ts cells consistent with their ability to mediate immunosuppression at distinct locations. Surprisingly, CD25+Ts cells are depleted of gut‐homing integrin α4+β7+ T cells, while being enriched in skin‐homing cutaneous lymphocyte antigen (CLA)+ T cells. These findings document heterogeneous homing potential of peripheral blood‐borne CD25+ Ts cells with marked skewing for skin‐ versus gut‐homing. Expression of CCR4 associates with both CD25 and CLA cell surface markers, being highest on CD4+CLA+CD25+ T cells. Importantly, CD4+CD25+ Ts cells isolated from human cord blood lack expressionof CLA while expressing CCR4, suggesting intrinsic expression of CCR4 on CD25+ Ts cells. These observations indicate that the increased expression of CCR4, which is proposed to guide CD25+ Ts cells to DC, is an intrinsic feature of CD25+ Ts cells.