Treatment of nephrotic syndrome associated with hepatitis B are controversial, but some patients may respond to interferon therapy. Steroid therapy in these patients could be limited, because it may aggravate hepatitis with the acute viral replication. Lamivudine may also be effective in reducing viral burden and may convert patients from HBsAg and HBeAg positive to negative. But there was no report for the usefulness of lamivudine in treatment of these patients. We performed a randomized comparative study to assess the usefulness of lamivudine and the effect of steroid in the use of lamivudine in treatment of B-viral associated nephrotic syndrome. Twelve patients(M:F=1:0.2, mean age 34.3 years, MCD 1, MPGN 5, MGN 6 patients) suspected to have the acute viral replication with nephrotic syndrome were included. They were randomly assigned to receive lamivudine and steroid combination therapy(group I, 150mg of lamivudine with high-dose steroid, 1mg/kg/day, orally once daily in 6 patients) or lamivudine alone therapy(group Ⅱ, 150 mg of lamivudine orally once daily alone in 6 patients). The duration of lamivudine use was 6 months in both groups, and that of steroid use was 6 weeks in group 1. Then, lamivudine and steroid were tapered according to the amount of proteinuria and serum HBV-DNA titer. All patients were closely monitored every 2 months with clinical, bioche mical, and serological parameters for 10 months. The rate of negative sero-conversion of HBV- DNA were 91.7%(11/12) at 2 months of lamivudine therapy in all patients, and there was no difference between group Ⅰ and Ⅱ(83.3% vs. 100%, p>0.05). In group I, there were a significant decreases of mean serum HBV-DNA values(899.2±711.9 vs. 31.4±32.7, 12.7±27.6, and 137.2±278.1pg/ml, p<0.05, respectively), proteinuria(11.0±3.6 vs. 3.9±2.3, 2.1±2.3, and 2.5±3.1g/d, p<0.05, respectively), and SGPT (57.7±18.9 vs. 30.5±12.4, 23.8±10.2, and 26.0±10.4 IU/L, p<0.05, respectively) measured at 2, 6, and 10months compared to before therapy, and serum albumin levels were significantly increased at 2, 6, and 10months compared to before therapy(2.2±0.5 vs. 3.1±0.5, 3.9±0.8, and 3.9±0.9g/dL, p<0.05, respectively). In group Ⅱ, serum HBV-DNA was significantly decreased at 2, 6, and 10 months compared to before therapy(358.8±369.3 vs. 19.1±27.0, 0.0±0.0, and 0.0±0.0pg/ml, p<0.05, respectively), and proteinuria and SGPT were significantly decreased at 6 and 10 months compared to before therapy(8.5±5.5 vs. 2.6±1.3 and 2.1±2.3g/d, p<0.05; 67.5±43.0 vs. 25.3±11.6 and 31.5±9.2IU/L, p<0.05, respectively). Serum albumin levels were significantly increased at 10 months compared to before therapy(2.8±0.8 vs. 4.3±0.1g/dL, p<0.05). Serum HBV-DNA levels rebounded in two patients of group Ⅰ, but none was observed in group Ⅱ. No serious adverse events were observed in all the patients. In conclusion, lamivudine and steroid combination therapy may more rapidly decrease proteinuria than lamivudine alone in B-viral associated nephrotic syndrome, but may induce the rebound of serum HBV-DNA.