The aim was to determine the influence of initial dose and dose per fractionation on retreatment tolerance of the kidney. Mouse kidney was bilaterally irradiated with various single or fractionated X-ray doses equivalent to about 12-70% of a defined response dose. The mice were retreated with a range of single doses after 2 or 26 weeks. The development of functional kidney damage was followed by monthly testing of clearance of 51CrEDTA until the animals expressed overt renal dysfunction (maximum follow-up 70 weeks after retreatment). Reirradiation tolerance was assessed by probit analysis and Kaplan-Meier actuarial estimates of the incidence of a defined level of renal damage at 40 weeks after retreatment. Doses required to give a 50% incidence of damage (RD50) were compared for animals that had received previous single dose or fractionated irradiations, or that were previously unirradiated. Multivariate analysis of time to expression of renal damage (latency) was also done using the Cox Proportional Hazards model. Results demonstrated that previous irradiation always compromised retreatment tolerance, even for intervals of 26 weeks after initial treatments with < 20% full response dose. Reirradiation tolerance was inversely related to the initial dose and tolerance decreased significantly with increasing interval between treatments, suggesting progression rather than recovery from the initial damage. Linear-quadratic analysis of the data for reirradiation at 26 weeks after partial-response doses gave an αbeta; = 1.4 Gy. This was significantly lower than the αbeta; = 3.3 Gy obtained for initial treatments alone (no retreatment), indicating a larger fractionation-sparing effect for the retreatment situation.