Although most childhood nephrotic syndromes respond to steroid treatment, steroid resistant nephrotic syndrome (SRNS) is also common and is particularly difficult to treat. This study investigated the role of glycosaminoglycans ( GAG) in the pathogenesis and clinical course of nephrotic syndrome in children. Thirty-four children ( 21 males and 13 females, mean age 3.7 +/- 1.6 years) with steroid-sensitive nephrotic syndrome and 20 children with steroid-resistant nephrotic syndrome ( 12 males and 8 females, mean age 10.9 +/- 3.8 years; of the twenty, four had primary SRNS (FSGS) and the others had secondary SRNS) were included the study. Mean urine levels of GAG relative to creatinine (UGAG/UCr) in patients with SRNS ( n= 20, 113.01 +/- 78.46 mg g(-1) Cr) and in patients experiencing the nephrotic period of steroid-sensitive nephrotic syndrome ( n= 34, 132.15 +/- 101.55 mg g(-1) Cr) were both significantly higher than mean U-GAG/U-Cr for control subjects ( n= 30, 51.83 +/- 47.66 mg g(-1) Cr) ( P< 0.01 for both). Patients excreted significantly more GAG during the nephrotic period of steroid-sensitive nephrotic syndrome than during remission ( 132.15 +/- 101.55 vs 39.11 +/- 42.73 mg g(-1) Cr, respectively; P< 0.01). There was, however, no significant difference between UGAG/UCr for patients with steroid-resistant nephrotic syndrome and U-GAG/U-Cr in the nephrotic period of steroid-sensitive nephrotic syndrome. Urine GAG excretion correlated significantly with the severity of proteinuria. The results suggest that GAG play a significant role in the pathogenesis of nephrotic syndrome but that GAG excretion is not a marker for response to steroid treatment in pediatric patients with this condition.