Increased pulmonary resistance may reduce survival and treatment options in patients with congestive heart failure. Nitric oxide (NO) is a determinant of normal pulmonary resistance vessel tone. We tested the hypothesis that loss of NO function contributes to increased pulmonary vascular resistance index (PVRI) in congestive heart failure. Pulmonary arterial resistance vessel function was studied in 25 conscious adults. Three groups were studied: 8 controls, 9 patients with congestive heart failure and normal PVRI, and 8 patients with congestive heart failure and raised PVRI. Segmental arterial flow was determined with a Doppler wire and quantitative angiography. N^G-monomethyl-l-arginine (l-NMMA) was used to inhibit NO, whereas phenylephrine was used as an endothelium-independent control. The response to inhibition of NO with l-NMMA was less in patients with congestive heart failure and elevated PVRI than in patients with congestive heart failure and normal PVRI (p <0.05). The difference in response between the congestive heart failure groups was specific to NO-dependent regulation because the response to the endothelium-independent constrictor phenylephrine was not different (p = 0.92). There was no difference in response to l-NMMA between controls and patients with congestive heart failure and normal PVRI. The response to l-NMMA correlated to PVRI. In adults with congestive heart failure, NO appears to play an important role in maintaining normal pulmonary resistance.