The use of low-dose total body irradiation (LTBI) in treatment of lymphomatous malignancies dates back to the 1920s. The usual practice was to give very low individual TBI fraction sizes (0.1-0. 25 Gy) several times a week to a total dose of 1.5-2 Gy. Despite this very low total dose, LTBI could induce long term remissions and was always as effective as the chemotherapy to which it was compared. In modern radiotherapy, LTBI is still a valid option in treatment of chronic lymphocytic leukaemia (CLL) and the advanced stages of indolent low-grade non-Hodgkin's lymphoma (NHL). Its use in the early stages of low-grade NHL is under investigation in a large multi-institutional trial. The efficacy of LTBI is believed to stem from three mechanisms, namely; immune-enhancement, induction of apoptosis, and the intrinsic hypersensitivity to low-radiation doses demonstrated in many cell lines and tumour systems. Thus, LTBI seems to provide 'alternative' mechanisms of action against cancer cells. This should encourage researchers to explore strategies that integrate LTBI in new and innovative experimental treatment protocols that explore the possible synergism between LTBI and chemotherapy, biological response modifiers and/or immunotherapy. The increased incidence of secondary leukaemia that occurs when LTBI is combined with alkylating agents and/or total lymphoid irradiation should be kept in mind when designing such protocols as it may limit the use of LTBI in highly curable diseases and young patients in whom long survival is expected.