We set out to determine whether any interaction occurs between BCNU and radiation for the mouse skin and spinal cord. Single doses of BCNU of 10, 20, or 30 mg/kg were injected intraperitoneally as a function of time before or after irradiation of the foot or spinal cord of anesthesized C3H mice. Enhancement of the radiation skin reaction (dose enhancement factor=1.3) was seen when BCNU (30 mg/kg) was given 1 day, 6 hr, and 2 hr prior to irradiation of the foot with 2,500 rad, and a larger DEF of 1.6 was observed when BCNU was given immediately before the radiation dose. However, with a different mouse strain (BALB/c) not anesthetized at the time of irradiation, no significant enhancement following a dose of 20 mg/kg BCNU was observed. Experiments are in progress to determine the cause of these differences BCNU (10 mg/kg) was given 24 hr or immediately prior to various single doses of radiation to a 12 mm segment of the mouse spinal cord (T 11–12 to L 1–2), and the subsequent myelitis was scored monthly. The addition of BCNU to irradiation did not accelerate the development of myelitis, nor the ultimate proportion of animals developing hind limb paralysis: the 50% myelitis dose at 10 months (MD 50/10 mo ) values for irradiation alone, BCNU at the time of irradiation and 24 hr before were 3,722, 3,795 and 3,853 rad, respectively.