Until recently endothelial nitric oxide synthase (eNOS) has been associated exclusively with physiological functions, particularly in the cardiovascular system. However, increasing evidence has been accumulated that supports the concept for a role of eNOS in pathophysiology. In particular, detection of eNOS protein and activity in human monocytes/macrophages suggest an immunomodulatory role of this enzyme. Here, we review data that promote the hypothesis that by enhancing TNFalpha production, eNOS activity should be regarded as a novel pro-inflammatory parameter in human monocytes/macrophages. (C) 2003 Elsevier Inc. All rights reserved.