Endothelium-derived nitric oxide is beneficial in experimental stroke. We assessed plasma NO levels in patients with acute stroke and their association with both severity and outcome. Plasma nitric oxide (NO), assessed as nitrate/nitrite (NOx), cyclic guanosine monophosphate (cGMP, second messenger to NO), L-arginine (substrate for NO) and L-citrulline (co-product with NO) levels were measured in 228 patients with acute ischemic stroke, 49 patients with acute hemorrhagic stroke, and 38 age and gender-matched normal volunteers. Stroke severity was assessed using the Glasgow Coma Scale, and the outcome was judged by discharge destination (home, institution, or dead). In our study, stroke patients had low levels of NOx (micromol/l): ischemic 49.9 (26.1); hemorrhage 41.7 (19.5); and control 64.0 (36.3) (P < .001); L-arginine (micromol/l): ischemic 85.1 (32.3); hemorrhage 69.9 (24.4); and control 104.0 (30.0) (P < .001); and L-citrulline (micromol/l): ischemic 30.5 (12.3); hemorrhage 26.7 (12.1); and control 39.4 (13.5) (P < .001). Cyclic GMP levels were elevated in stroke: ischemic 21.2 (16.1); hemorrhage 24.7 (17.5); and control 15.8 (9.2) (P = .024). Patients who died or became institutionalized had lower NOx, L-arginine, and L-citrulline levels, and higher cyclic GMP levels, than patients who were discharged home. NOx levels were not associated with feeding status in patients. Low levels of NOx are present in stroke and are associated with severity and outcome. Because endothelium-derived NO is beneficial in acute stroke, administering NO might be beneficial in acute stroke.