Recent studies have suggested that cell adhesion plays an important role in the development and regulation of inflammation. To elucidate the mechanisms of regulation of adhesion molecule expression by cytokines in psoriatic lesions, we compared the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and P-selectin immunohistochemically in involved and uninvolved psoriatic skin with the expression of these molecules in normal skin, and measured the amounts of tumor necrosis factor-alpha, interferon-gamma, interleukin-1alpha, and interleukin-1beta in the supernatant of freeze-thawed skin specimens using an enzyme-linked immunosorbent assay. There was strong staining for P-selectin on endothelial cells from involved skin. There was also strong staining for intercellular adhesion molecule-1 on keratinocytes, dermal infiltrates, and endothelial cells from involved skin and on endothelial cells from uninvolved skin, and strong staining for vascular cell adhesion molecule-1 on dermal dendritic cells and fibroblasts and for E-selectin on endothelial cells from involved skin. Large amounts of tumor necrosis factor-alpha were detected in six out of ten specimens of involved skin, but not in uninvolved or normal skin, although interferon-gamma was detected in both involved and uninvolved skin to the same extent. Neither interleukin-1alpha nor interleukin-1beta was detected in involved skin. There was strong staining for tumor necrosis factor-alpha on keratinocytes and endothelial cells from involved skin. These findings suggest that tumor necrosis factor-alpha might play an important role in the induction of vascular adhesion molecules in psoriatic lesions.