The majority of T cells in lesional psoriatic skin express the skin homing receptor, cutaneous lymphocyte-associated antigen (CLA). We investigated whether this reflects the selective migration of CLA positive cells into evolving psoriatic plaques, consistent with an important role in disease onset, or whether this occurs in the context of an established cutaneous inflammatory response. We identified the advancing edge of plaques in 16 patients with chronic plaque psoriasis using scanning laser Doppler fluxmetry, and performed immunohistochemical analysis of i) lesional psoriatic skin, ii) clinically normal skin immediately in front of the advancing plaque edge, and iii) uninvolved skin distant from the plaque edge. The T-cell infiltrate was characterized using monoclonal antibodies to CD3, CLA and the integrin alphaEbeta7, which is associated with the retention of lymphocytes at mucosal sites. Epithelial proliferation was assessed using a monoclonal antibody to the nuclear proliferation marker Ki67. There was enrichment of CLA positive T cells in evolving psoriatic skin compared to distant, uninvolved skin (mean CLA positive 75.9% vs 47.8%; P<0.003). This accumulation of CLA positive cells occurred before epidermal hyperproliferation was evident, suggesting that this population of cells plays an important, early role in disease pathogenesis. Established lesional psoriatic skin contained a mixed infiltrate of CLA positive (mean 53.2%) and alphaEbeta7 positive (mean 18.2%) cells, suggesting less tissue-specific T-cell infiltration, although an additional, specific role for alphaEbeta7 in cutaneous inflammation cannot be excluded. Furthermore, this study has highlighted scanning laser Doppler fluxmetry as a useful investigative tool, permitting analysis of the earliest and therefore potentially most important changes in psoriatic plaque formation.