In November 2009, a 3-year-old boy presented to our Emergency Department with a 4 day history of progressive feet, legs and periorbital edema. Together with edema, his body weight increased from 14.3 Kg to 17.2 Kg. Medical history included recurrent urinary tract infections and two weeks earlier an upper respiratory tract infection, characterized by cough, sore throat, and nasal congestion, spontaneously solved in 3 days. Physical examination showed remarkable finding of generalized anasarca. Blood pressure was normal. Initial urine analysis showed heavy proteinuria (6.67 g/l), confirmed by the 24-hour urine collection which showed a concentration of protein of 8.5 g/l. Other laboratory findings included hypoproteinemia (4,8 g/dl), low serum albumin (2.0 g/dl), hypercholesterolemia (440 mg/dl), elevated low-density lipoprotein cholesterol (238 mg/dl) and hypertriglyceridemia (230 mg/dl). Urinary sediment showed mild microhematuria (6-10 erythrocytes per field) and rare granulated cylinders. The nasopharyngeal swab was taken. Tests including C3 and C4 complement levels, C-reactive protein, serum creatinine, blood urea nitrogen were normal or undetectable. The clearance of the creatinine at the time of diagnosis was 111 ml/min. RT-PCR over the nasopharyngeal swab was performed since he reported respiratory symptoms and since influenza A/H1N1 was epidemic in Italy in that season; it resulted positive for influenza A/H1N1. NS was treated with fluid restriction, low sodium diet and prednisone 60mg/m per os daily. Blood pressure, body weight and water balance were daily monitored. Since serum albumin decreased (1.3 g/dl), an infusion of 50 ml of albumin 25% was given, followed by an intravenous bolus of 17 mg furosemide. Interestingly, 24 hours later, the patient was noted to have an increase of the periorbital edema and developed bilateral scrotal hydrocele. Nasopharyngeal swab was positive for influenza A/H1N1 virus and a therapy with oseltamivir 60 mg twice daily was also started. Over the next 48 hours, the patient achieved significant clinical improvement of his anasarca-related symptoms. Laboratory tests executed after 10 days of corticosteroid therapy showed increasing serum proteins (6.2 g/dl) and serum albumin (3.5 g/dl), together with a concentration of proteins lower than 0.07 g/l in the 24-hour urine collection. Weight at discharge was 14.400 Kg. According to the latest guide-line on the management of childhood onset NS, treatment with prednisone was reduced to 40 mg/m on alternate days after 6 weeks and prolonged for further 6 weeks, then suspended without tapering[]. Clinical conditions and laboratory tests at suspension were normal and no side effects of corticosteroid therapy were reported. Clinical and laboratory follow-up performed monthly for the first 3 months and than at 6 and 12 months after discharge showed no relapse of NS or respiratory complications.