In the development of atherosclerosis, inflammatory cells adhere to and migrate into the vascular walls by interacting with vascular smooth muscle cells. To investigate the mechanism of aspirin's anti-atherogenic activity, we examined whether aspirin inhibits the adhesion of lymphocytes to human aortic smooth muscle cells (AoSMC). Aspirin inhibited T-cell adhesion to AoSMC activated by interleukin 1beta (IL-1beta) in a dose-dependent manner. Antibodies to the adhesion molecules ICAM-1 or VCAM-1, but not to E-selectin, prevented T-cell adhesion. ICAM-1 and VCAM-1 expression stimulated by IL-1beta was reduced by the treatment with aspirin, whereas the expression of E-selectin was unaffected. Nuclear factor kappaB (NF-kappaB) activity was enhanced by IL-1beta and reduced by aspirin, indicating that decreased ICAM-1 and VCAM-1 expression was due to reduced NF-kappaB activity.Thus, aspirin inhibits the adhesion of Jurkat T cells to IL-1beta-activated AoSMC by reducing NF-kappaB activity and decreasing expression of ICAM-1 and VCAM-1, and may prevent the development of atherosclerosis.