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 (U(GAG)/U(Cr)) 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 U(GAG)/U(Cr) 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.