time of appearance of injury became generally acknowledged after publication of the Christie Hospital experience with abdominal irradiation (1). The overall incidence of nephropathy in patients treated between 1948 and 1961 for seminoma or ovarian cancer metastases was high: 20/54 developed acute nephritis at 6 to 13 months after irradiation, and chronic nephritis was seen in 25/54 patients at 1.5 to 4 years. Benign hypertension and late malignant hypertension were also reported at 1.5 to 5 years and 5 to 19 years, respectively (2). There was a high incidence of renal damage for total in excess of 28 Gy, and about onethird of the patients developed renal damage after 23 Gy in 24 to 30 fractions to both kidneys. These results still form the basis of modern accepted tolerance doses to the human kidney, and they established the need for very long follow-up times to adequately assess renal damage (particularly renal hypertension). This was later confirmed by Thompson et al. (3), who reported a mean latency of 9 years for the development of nephritis or hypertension after irradiation of the stomach for peptic ulcers. More recently, several investigators have used sensitive, external scintigraphic scanning techniques to investigate renal function after irradiation, and two prospective studies (4, 5) reported functional tests with a follow-up of at least 5 years. Kim et al. (4) identified unilateral nephropathy, with a latency of 4 months to 1.5 years, in 9 of 18 patients treated for non-Hodgkin's lymphoma (NHL) with total of 22 to 45 Gy to the whole or half of the left kidney (the total dose to the right kidney was <15 Gy). Dewit et al. (5, 6) reported on 26 patients who were evaluated prospectively for renal function after total or partial renal irradiation. The NHL patients received a total of 40 Gy to the whole of the left kidney and 12 to 13 Gy to the right kidney. Left renal glomerular and tubular function in this group decreased progressively, to 25 and 31% of pretreatment values, respectively, at 6 to 9 years. There was a smaller decrease in renal function of Hodgkin's cancer patients who received similar to only 30-50% of the left kidneys. Eight of 15 patients with documented renal injury also developed hypertension, presumably of renovascular origin, at 1 to 7 years after irradiation (7). The above pattern of progressive deterioration of renal function over very long periods after irradiation is entirely consistent with the picture which emerges from animal models. Numerous studies have demonstrated progressive, radiation dose-dependent decreases in glomerular filtration rate (GFR) and estimated renal plasma flow (ERPF), polyuria, anemia and hypertension in rodent and pig models (see refs. 8, 9 for review). The time of onset of overt functional damage is clearly inversely related to radiation dose and may be longer than 1 year after low (10-12). The progressive nature of radiation-induced renal nephropathy means that any estimate of renal tolerance must be qualified by stating the expected observation period. The absence of measurable renal dysfunction at fairly short follow-up times therefore cannot be equated with a lack of damage. Re-treatment studies in experimental animals have indeed demonstrated that even low subthreshold radiation doses, which do not themselves lead to overt renal dysfunction within the animal's life span, cause permanent and even progressive occult damage which leads to decreasing reirradiation tolerance with increasing time from the first treatment (11, 13-16). These results could have impor11 invited our three overseas Editorial Advisors to write an editorial