The cause of childhood nephrotic syndrome (NS) is unknown and whether it responds to steroid therapy remains unpredictable. In the present study, we measured the Th1/Th2 cytokines, serum tumor necrosis factor-beta (TNF-beta) and interleukin-13 (IL-13), levels in children with NS before and after prednisolone (60 mg/m(2)/day) treatment for 4 weeks, to evaluate their relationships with disease activity and treatment response. Patients with acute NS had higher serum TNF-beta and IL-13 levels than normal controls. After 4 weeks of prednisolone treatment, patients with steroid-resistant NS (SRNS) presented a higher serum TNF-beta level than that before treatment (p=0.008). In contrast, patients with steroid-sensitive NS (SSNS) presented a higher serum IL-13 level than that before treatment (p=0.027). This study demonstrates the significance of serum TNF-beta and IL-13 levels in relation to the disease activity and treatment response of childhood NS. Patients with SRNS appeared to have elevated TNF-beta after steroid therapy, while patients with SSNS tended to have elevated IL-13 after steroid therapy. Thus, an altered Th1/Th2 reaction as demonstrated by TNF-beta/IL-13 imbalance may play a pathophysiologic role in childhood NS.