The incidence of de novo malignancy was analyzed in 274 renal transplant recipients whose graft had functioned for at least 3 years and who had been followed for 2622 patient-years and individually for up to 29 years. The actuarial incidence and relative risks (RR) of tumor development (compared with National statistics) were calculated. Subgroup analysis was performed according to age, sex, the number of years and type of immunosuppression, and the tumor type. Seventy one tumors occurred in 54 patients. Skin tumors were the most common, followed by lymphoma, renal, bladder, and bronchial carcinoma. The actuarial cumulative risks of tumor development were 18.4% (95% confidence interval [CI] 12.4-24.3%) at 10 years and 49.6% (95% CI 36.3-62.0%) at 20 years. The overall RR of developing a tumor was 6.2 but was higher for men (RR 7.3) than women (RR 4.9). The RR of developing skin cancers, but not other malignancies, increased from 6.6 at 5 years to 20 after > 15 years. There was no evidence that cyclosporine-treated patients had an increased incidence of tumors, indeed the risk may be less in patients treated with cyclosporine and low-dose azathioprine than in those treated with azathioprine and prednisolone alone after more than 5 years.