['To investigate the role of neuronal nitric oxide synthase (NOS1) in murine polymicrobial peritonitis and sepsis.', 'Randomized experimental trial.', 'Animal research facility.', 'B6129S NOS1+/+ and B6;129S4 NOS-/- mice.', 'NOS1+/+ and NOS1-/- animals underwent cecal ligation and puncture (CLP) or sham surgery and received the NOS1 inhibitor 7-nitroindazole (7-NI) or vehicle.', 'After CLP, genetic deficiency and pharmacologic inhibition of NOS1 significantly increased risk of mortality [8.69 (3.27, 23.1), p<0.0001 and 1.71 (1.00, 2.92) p=0.05, hazard ratio of death (95% confidence interval) for NOS1-/- and 7-NI-treated NOS1+/+ respectively] compared with NOS1+/+ animals. In 7-NI-treated NOS1+/+ animals, there were increases (6 h) and then decreases (24 h), whereas in NOS-/- animals persistent increases in blood bacteria counts (p=0.04 for differing effects of 7-NI and NOS1-/-) were seen compared with NOS1(+/+) animals. After CLP, NOS1(-/-) had upregulation of inducible NOS and proinflammatory cytokines and greater increases in serum tumor necrosis factor-alpha and interleukin-6 levels compared with NOS1+/+ mice (all p<0.05). Following CLP, there were similar significant decreases in circulating leukocytes and lung lavage cells (p<or=0.0008) and significant increases in peritoneal lavage cells (p=0.0045) in all groups. Over 6 h and 24 h following CLP, compared with NOS1+/+, NOS-/- mice had significantly higher peritoneal cell concentrations {respectively 0.40+/-0.09 vs 0.79+/-0.15 [log(x10(4)cells/ml)] averaged over both times p=0.038}.'] Does neuronal nitric oxide synthase deficiency decrease survival in bacterial peritonitis and sepsis?