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Background The association between HLA class II and frequent relapse of nephrotic syndrome (FRNS) has been reported. Objective To identify the association between HLA class II, history of atopy, and upper respiratory tract infection (URTI) with FRNS. Methods This was a case control study conducted at the Department of Child Health, Hasan Sadikin Hospital Bandung and Cipto Mangunkusumo Hospital Jakarta from November 2002 to October 2003 on children aged 1-14 years with FRNS. The subjects consisted of 40 FRNS and 84 healthy children. HLA class II was typed by polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) in Leiden, the Netherlands. The association between HLA class II and FRNS was expressed by odds ratio (OR). The association between such factors and FRNS was analyzed by logistic regression. Results Atopy was higher in patients than that in controls (P=0.013). URTI did not differ in both groups (P=0.173). HLA- DRB1*03 and DRB1*04 (OR=4.43, P=0.03), DQB1*02 (OR=3.43, P=0.00), and DQB1*04 (OR=12.06, P=0.01) were significantly higher among patients than those in controls whereas HLA-DRB1*12 (OR=0.34, P=0.02) and DQB1*0301p (OR=0.35, P=0.02) were significantly lower among patients than those in controls. Using logistic regression analysis, only HLA- DRB1*12, DQB1*02 and atopy took part in FRNS. Conclusion HLA-DRB1*12, DQB1*02, and atopy all together have association with FRNS.