Objectives: This study was conducted to find if there is any alternation in the synthesis of endotheial-derived relaxing factor nitric oxide (NO) and in lipid peroxidation in childhood nephrotic syndrome. Both mechanisms are claimed to have a role in the pathogenesis of immunologically-mediated renal injury and both are reported to interact with one another. Methods: The stable metabolite of NO, urinary nitrite, and the degradation product of lipid peroxide, serum malondialdhyde (MDA) together with serum creatinine, blood urea nitrogen (BUN) and urinary protein in 24 hour urine were estimated in 10 healthy control children (Group 1) and in 47 children suffering from different forms of the nephrotic syndrome: Minimal change nephrotic syndrome (MCNS) at first presentation (Group II, 10 cases), in remission (Group III, 10 cases), in relapse (Group IV, 10 cases) and focal segmental glomerulsclerosis (FSGS) (Group V, 8 cases) and membranous glomerulonephritis (MGN) (Group VI, 9 cases). Results: Our results showed significantly higher levels of urinary nitrite in patients with MCNS versus controls and children with FSGS or MGN. The urinary nitrite level was 3.5 +/- 1.3 umol/L in the controls, 9.2 +/- 1.7 umol/L  in Group II (P ˂0.001), 7.0 +/-1.8 umol/L in Group III (P ˂ 0.001), 10.6 +/-1.6 umol/L in Group IV (P ˂ 0.001), 3.08 +/-1.3 umol/L in Group V (pNS) and  3.38 +/- 0.9 umol/L in Group VI (pNS).  The urinary nitrite levels showed no significant correlation to the 24 hour urinary protein in all patients (r=0.163, p ˃ 0.05). On the other hand serum MDA showed significantly higher levels in all patients groups (Group II: 2.8 +/- 0.96 umol/L; Group III: 1.61 +/-0.46 umol/L; Group IV: 2.38 +/-0.86 umol/L; Group V: 4.06 +/- 1.11 umol/L and Group VI: 4.42 +/- 1.25 umol/L) compared to controls (0.73 +/- 0.29 umol/L) (p ˂ 0.001). The increase was maximum in FSGS and MGN and least in MCNS. There was a strong positive correlation between serum MDA and hour urinary protein (r = 0.584, p ˂ 0.001). Conclusions: 1)-The measurement of urinary nitrite excretion may be useful in differentiating MCNS from FSGS and MGN. 2)-NO may play a protective role in cases of MCNS as indicated by the higher urinary nitrite levels. 3)-The continuous production of NO in MCNS even in remission may serve to scavenge small fluxes of superoxide radical produced by endothelial cells. 4)-Lipid peroxidation may play a major role in the production of proteinuria and in the pathogenesis of the nephrotic syndrome.