Factors that may account for the increased risk of malignant disease in allograft recipients include antigenic stimulation by the allograft, reactivation of oncogenic viruses, and depletion of natural killer lymphocytes. In adults, malignancies complicate about 5% of renal transplantations, and the risk of cancer approximates 10% after ten years. The most common malignancies are skin cancer (40%), which occur after a mean of ten years; lymphoproliferative disorders (LPD, 15%), after a mean of 33 months; Kaposi's sarcoma, after a mean of 20 months; and vulvoperineal carcinomas complicating condylomatosis, after a mean of 12 years. In children, only about 1% of transplant procedures are followed by development of a malignancy, which is an LPD in 27 to 75% of cases. In a study of 873 kidney transplants performed in subjects younger than 18 years, the incidence of malignancy was 0.8%, versus 6.9% in 43 patients who were older than 18 years at transplantation. Of the ten malignancies in the pediatric group, two were LPDs (20%), two were liver carcinomas complicating hepatitis B or C, two were Kaposi's sarcomas, one was a urinary bladder carcinoma after long-term cyclophosphamide therapy, one was a carcinoma of the vulva and cervix, and two were unclassified tumors of the meninges and ovary. None of the pediatric patients developed skin cancer, although follow-up was longer than ten years in 157 patients. Half the malignancies were fatal (one LPD, one Kaposi's sarcoma, the two liver cancers and the bladder cancer). One or more risk factors were identified in seven of the ten patients, including oncogenic viruses (HBV, HCV, EBV, HPV) severe immunodepression (OKT3++), and a history of oncogenic chemotherapy. Prevention of malignancies in renal transplant recipients currently relies on caution in the use of immunosuppressants and early detection of premalignant lesions, and in the future may benefit from the development of antiviral drugs.