Acquired deficiency of anticoagulant proteins, due to loss in the urine, has been proposed as one of the major thrombogenic alterations in nephrotic syndrome (NS). Protein Z (PZ) is a single-chain vitamin K-dependent glycoprotein. Low PZ levels are reported to be a risk factor for thrombosis. The aim of this study was to investigate protein Z and other natural anticoagulant levels in children with NS. Thirty children aged between 1.5 and 12 years with NS (Groups I and II) and 19 age- and-sex-matched healthy controls (Group III) were enrolled into the study. Patients were divided into two groups: Group I (proteinuria > 40 mg/ m(2)/ hr) and Group II (patients in remission). Plasma PZ levels in Group I were significantly lower than Group II (p = 0.009) and group III (p = 0.018). Plasma levels of AT III for Group I were significantly lower than for Groups II and III (p = 0.009, p = 0.005, respectively). Protein C levels in Group I were higher than in Group II and Group III (p = 0.002, p = 0.000, respectively). Protein Z levels positively correlated with serum total protein and albumin levels (p = 0.003, p = 0.003, respectively) and negatively with the degree of proteinuria (p= 0.000). Protein Z levels were positively correlated with AT III (r = 0.037, p = 0.04). Along with the other coagulation abnormalities, decreased protein Z may contribute to increased risk of thromboembolic complications in children with NS. The negative correlation between proteinuria and PZ level suggests the possibility of renal PZ loss. Further studies are needed to investigate the mechanism and role of decreased PZ in NS.