A total of 65 patients with von Hippel-Lindau disease underwent surgery for renal cell carcinoma (54 bilaterally and 11 unilaterally) at 8 medical centers. Only 1 patient presented with metastatic disease. Radical nephrectomy and nephron sparing surgery were performed in 16 and 49 patients, respectively. Mean posttreatment followup was 68 months. The 5 and 10-year cancer-specific survival rates for all patients were 95% and 77%, respectively. The corresponding rates for patients treated with nephron sparing surgery were 100% and 81%, respectively. Of the latter patients 25 (51%) had postoperative local tumor recurrence but only 2 had concomitant metastatic disease. Survival free of local recurrence was 71% at 5 years but only 15% at 10 years. End stage renal failure occurred in 15 patients (23%): 6 underwent renal transplantation (5 are alive with satisfactory renal function and no evidence of malignancy) and 9 were treated with chronic dialysis (6 are free of tumor). Our results indicate that nephron sparing surgery can provide effective initial treatment for patients with renal cell carcinoma and von Hippel-Lindau disease. These patients must be followed closely, since most will eventually have locally recurrent renal cell carcinoma. When removal of all renal tissue is necessary to achieve control of malignancy, renal transplantation can provide satisfactory replacement therapy for end stage renal disease.