Neutrophil-derived proteinases cause glomerular injury by proteolysis of the glomerular basement membrane and alterations in glomerular metabolism. Recently, a marked elevation of the plasma elastase complex with α1-proteinase inhibitor (α1-PI) both in the acute phase and during remission of nephrotic syndrome (NS) compared with age-matched controls was reported. In experimental immune-mediated glomerulonephritis ε-aminocaproic acid (EACA) significantly reduced albuminuria, and it was suggested that this may be linked with the antiproteolytic activity of the drug. We studied plasma antithrombin III (AT-III), α1-PI, α2-antiplasmin (α2-A), α2-macroglobulin (α2-M) activity, and some blood coagulation and fibrinolysis tests in children with frequently relapsing prednisone-responsive NS. Also, the effect of prednisone alone (Group I, n = 9) and prednisone plus EACA (Group II, n = 10) treatment regimens on the studied parameters was estimated. All investigations were performed on admission to the hospital and after approximately 13 days of prednisone alone therapy (Group I), as well as before the administration of prednisone plus EACA and 24 hours after the last dose of EACA, ie, after approximately 5 days of treatment (Group II). Prednisone was administered at the usual dose of approximately 2 mg/kg/d and EACA was given orally at the doses of 72 to 230 mg/kg of body weight per day for 3 to 10 days. In the acute phase of disease, NS patients (n = 19) were shown to have a statistically significant decrease of plasma AT-III (16.4 ± 4.7 vs. 21.9 ± 2.5 IU/mL) and α1-PI (1.28 ± 0.6 vs. 1.97 ± 0.34 IU/mL) activity, as well as a marked increase in plasma α2-M activity (14.96 ± 5.81 vs. 9.6 ± 1.6 IU/mL), and fibrinogen concentration (5.51 ± 1.78 vs. 2.96 ± 0.34 g/L) compared to the age-matched controls; no significant changes in plasma α2-A activity, plasminogen concentration, euglobulin clot lysis time, activated partial thromboplastin time (APTT), or thromboplastin time were noted. In children treated with prednisone alone, a marked increase in plasma AT-III (by 76%, P < 0.001) and α2-A (36%, P < 0.019) activity, and a significant decrease of the plasma fibrinogen concentration (6.07 ± 1.66 vs. 3.17 ± 1.64 g/L, P < 0.001), and APTT (45.1 ± 7.6 vs. 33.8 ± 4.4 s, P < 0.001) were found. Prednisone plus EACA therapy resulted in a significant increase in plasma AT-III activity (by 53%, P < 0.003), whereas plasma fibrinogen concentration and APTT remained unchanged. However, statistically significant differences between the pre-and posttreatment plasma AT-III, α1-PI, and α2-A activities in these patients were observed. There was also a relationship between EACA dose and the percentage change in plasma α2-A activity. In a few patients receiving prednisone plus EACA regimen, side effects that included purulent rhinitis, pharyngitis, increases in body temperature, loose stools, and an approximately 20% to 30% decrease in systolic and diastolic arterial blood pressure were observed. Thus, although the prednisone plus EACA treatment regimen seems to offer new therapeutic possibilities in some patients with NS, it should not be used in acute phase of the disease.