Nitric oxide is thought to be involved in blood pressure regulation. Nitric oxide synthase (NOS) genes are logical candidates for genetic hypertension. Of the three known forms of NOS, the "neuronal" and "inducible" Nos genes have been tested as candidate genes for causing inherited hypertension in Dahl salt-sensitive rats. In the present work, we analyzed the endothelial Nos gene, designated Nos3, directly and indirectly for cosegregation with blood pressure in six F2populations independently generated from crosses of Dahl salt-sensitive rats with rats of various other strains. The Nos3 alleles did not cosegregate with blood pressure in these populations. Therefore, Nos3 is an improbable, if not impossible, candidate gene for causing hypertension in the Dahl salt-sensitive rat. (Hypertension. 1997;29:49-52.)