The medical records of patients receiving cyclophosphamide for lupus nephritis between 1987 and 1993 at the New York University/Hospital for Joint Diseases Lupus Study Group Institutions were retrospectively reviewed. We identified 45 patients (38 female, seven male) who received a mean of 9 +/- 1 (range 2-23) pulses of intravenous cyclophosphamide for diffuse proliferative glomerulonephritis (n = 28), focal proliferative glomerulonephritis (n = 7), membranous nephropathy (n = 5), mesangial nephropathy with sclerosis (n = 1) or nephritis without biopsy (n = 4). Forty-two of the 45 patients received cyclophosphamide after failing steroid therapy. During a follow-up period of 52 +/- 3 months, nine patients progressed to end-stage renal disease (ESRD) with three additional patients experiencing a doubling of the creatinine and two patients persistent nephrotic range proteinuria. There were no deaths directly attributable to cyclophosphamide and no patients developed hemorrhagic cystitis or malignancy. Ten of 37 women had ceased menstruating prior to cyclophosphamide therapy. Treatment-associated amenorrhea occurred in only three patients all over 27 years of age. Intermittent intravenous cyclophosphamide therapy of lupus nephritis is well tolerated and usually effective in maintaining renal function in patients unresponsive to steroids although, in our experience, 20% of patients developed ESRD and a total of 14 of 45 (30%) patients had unsatisfactory outcomes.