Inflammatory skin disorders such as psoriasis show a preferential epidermal infiltration of neutrophils and T lymphocytes. This observation raises a question as to which factors determine the appearance and composition of leukocyte tissue infiltrations. Previously, we described a low molecular mass calcium-binding protein (psoriasin, molecular mass 11,457 Da, pI 6.77) belonging to the S1OO family that is highly upregulated in psoriatic keratinocytes and whose expression patterns implied a role in the inflammatory response. Here we report that human psoriasin is a potent and selective chemotactic inflammatory protein for CD4+ T lymphocytes and neutrophils at concentrations of about 10(-11) M. Psoriasin is not structurally related to the alpha or the beta chemokine subfamilies or to lymphotactin, a member of a newly described class of chemokines. Thus, we have observed a chemotactic protein outside the chemokine subfamilies that could be an important new inflammatory mediator.