Nephrotic proteinuria in minimal change disease (MCD) is supposed to be due to a circulating factor of immunologic origin. End-stage renal failure occurs if both steroids and immunosuppressive drugs remain ineffective. Three children (2 years, 3 years, and 6 years of age) with secondary steroid-resistant nephrotic syndrome (NS) were included, as they remained resistant to 30 days of treatment with prednisone (60 mg/m(2) per day), three pulses of methylprednisolone (1 g/1.73 m(2)) followed by oral administration of CyA 7.5 mg/kg per day over 2 months, and 1 month of intravenous (i.v.) administration of cyclosporine (blood level 500-600 ng/ml). All three patients were partially responsive to methylprednisolone pulses, with an increase of serum albumin by 100%. They were treated with plasma exchanges, cyclophosphamide and cyclosporine A, both given orally, pefloxacin and methylprednisolone pulses followed by orally administered prednisone. All three patients went into remission within 2 to 5 weeks. The character of their NS changed to a steroid-sensitive one. There were no significant side effects from the therapy. They had normal renal function, normal blood pressure and no residual proteinuria. A combination of plasmapheresis and multiple immunosuppressive medications was effective in producing remission of minimal change NS in three children who were previously resistant to glucocorticoids and cyclosporine.