The pulmonary vascular endothelium plays a critical role in lung inflammation. As a result of proinflammatory cytokine expression, adhesion molecules are upregulated on the surface of the endothelial cells. Adhesion molecules facilitate recruitment of leukocytes and thus, have been targeted for potential anti-inflammatory strategies. Prior induction of the stress response through thermal stimulation, or heat shock, alters proinflammatory gene expression by attenuating NF-kappaB signaling. As intercellular adhesion molecule-(ICAM) 1 expression is, in part, NF-kappaB-dependent, we hypothesized that heat shock would inhibit ICAM-1 expression. Heat shocking endothelial cells resulted in heat shock protein (HSP) expression as measured by HSP-70 induction, and decreased TNF-alpha-induced ICAM-1 expression in a manner that appeared to be transcriptionally mediated. Following heat shock, decreased TNF-alpha-induced NF-kappaB activation was observed and was associated with preservation of IkappaB-alpha and a decrease in phosphorylated IkappaB-alpha that correlated to inhibition of I kappa kinase (IKK) activity. Interestingly, exposing respiratory epithelial cells to heat shock, which results in NF-kappaB inhibition, did not affect TNF-induced ICAM-1 expression. We conclude that heat shock decreases endothelial cell ICAM-1 expression via inhibition of IKK activity.