Patients with steroid-resistant focal and segmental glomerulosclerosis (FSGS) have a poor prognosis but may benefit from high-dose methylprednisolone or cyclosporine A therapy. Ten patients were treated with a protocol of methylprednisolone infusions for 8 weeks followed by a combination of cyclosporine A and alternate-day prednisone for maintenance of remission for 2 weeks. Eight of ten patients remitted the nephrotic syndrome within 8 weeks of beginning treatment. One patient remitted edema but remained proteinuric, and one did not respond. After observation for 12-24 months, seven patients maintained remission with normal glomerular filtration rate. One non-responder had renal insufficiency and one patient had secondary non-response and end-stage renal disease. No patients developed hypertension. One patient had the diagnosis of Hodgkin disease made after 10 months of therapy. Follow-up renal biopsy in four patients showed no evidence of progressive interstitial disease. There were no other major side effects. Steroid-resistant FSGS may be successfully treated with the described protocol. Additional studies will be needed to determine if this approach prevents progression of renal disease.