The development of renal transplantation in the 1960s, made possible by azathiopine, also allowed the testing of the immunosurveillance proposed by Burnett and Thomas, that cancer has its origins in mutations which would usually be eliminated by a healthy immune system. An increased incidence of non-Hodgkin's lymphoma (NHL) in transplant recipients was soon recognised but not the generalised increases of malignancy that seemed to be predicted by the theory. Instead, increases of skin, liver, and (possibly) cervix cancers, and of Kaposi's sarcoma suggested that immunosurveillance operates primarily against malignancies of infective origin, as animal work had also indicated. It has become clear that this hazard is a feature of other immunosuppressive drugs, including 6-mercaptopurine, cyclophosphamide, cyclosporine, and methotrexate, and is not dependent on the presence of foreign antigens, extending to patients without organ transplants. In fact, an increased incidence of NHL has been found in virtually every type of marked immune impairment (whether or not treatment related) that has been studied in appreciable numbers, included AIDS and rare genetically determined disorders such as the Wiskott Aldrich syndrome.1

The paper by Farrell and colleagues2 in this issue ofGut on the risk of cancer in 782 …