OBJECTIVES: The objective of this study was to define the frequency and severity of steroid-related behavioral side effects in children with steroid-sensitive idiopathic nephrotic syndrome (SSNS) during treatment for relapse. STUDY DESIGN: We conducted a prospective, repeated- measures study in which 10 children with SSNS underwent behavioral assessment using the Child Behavior Checklist at baseline and during high dose prednisone therapy for relapse. RESULTS: Of the 10 children, 8 had normal behavior at baseline. Of these 8 children, 5 had Child Behavior Checklist scores above the 95th percentile for anxious/depressive behavior and/or aggressive behavior during relapse. Such scores are in the range normally considered appropriate for referral to a mental health provider. The 2 children who had abnormal behavior at baseline also experienced a worsening of their behavior during relapse. The behavioral changes occurred almost exclusively at prednisone doses of 1 mg/kg every 48 hours or more. Regression analysis showed that prednisone dose was a strong predictor of abnormal behavior, especially increased aggression. CONCLUSION: Children with SSNS often experience serious problems with anxiety, depression, and increased aggression during high-dose prednisone therapy for relapse.