The 5' promoter region of endothelial cell nitric oxide synthase (ecNOS) gene has several features which are compatible with a constitutively expressed, so called "housekeeping" gene. These include absence of a TATA box and the presence of Sp1 binding sites situated near the transcription start site. The promoter also contains sequences which suggest that it may be regulated by a variety of transcription factor-mediated signals. Studies of cultured endothelial cells show that ecNOS expression is modulated by shear stress, transforming growth factor beta, inhibition of protein kinase C, and the state of proliferation. These experiments indicate that although the ecNOS is a "constitutively expressed" gene, its content in the endothelium is subject to modest degrees of regulation which may have important physiological and pathophysiological implications.