Background: Neopterin (NP) is a pyrazino-pyrimidine compound derived from guanosie 5′-triphosphate. NP production has been linked to the activation of cell-mediated immunity. Increases in serum NP concentration and urinary NP excretion have been used as diagnostic markers in various immune-mediated clinical conditions including allograft rejection, infectious diseases autoimmune diseases, and neoplastic diseases. Objectives: To assess the changes that occur in serum neopterin levels in children with primary nephrotic syndrome (PNS). Methods: Serum NP levels were measured by ELISA in 38 children with active PNS (27 males, 11 females; aged 6.4 ± 2.9 years) (Group I) and 17 children (11 males, 6 females; aged 7 ± 2.5 years)with PNS in remission (Group II) and 20 age-and sex matched controls. All patients had normal creatinine clearance. Among Group I children, 28 patients were steroid-sensitive (SSNS) while 10 patients were steroid-resistant (SRNS). Results: Serum NP levels were significantly elevated in Group I patients (median =7.5, range 1.8-10.8 ng/ml) compared to Group II (median = 1.5, range 0.5-2.5 ng/ml, p ˂0.001) and controls (median = 0.6, range 0.1-2.7 ng/ml, p ˂ 0.001). Group II patients had similar NP levels compared to controls (p = 0.71). There was a significant positive correlation between serum NP levels and the degree of proteinuria in Group I patients (r = 0.4, p = 0.01). No significant differences in serum NP levels were noted between SSNS and SRNS patients (p = 0.4). Conclusions: Serum NP could be used as a marker of the activity of PNS but it could not be used to differentiate between SSNS and SRNS.