OBJECTIVE To assess the latent time, survival and dose-fractionation factors associated with permanent radiation myelopathy following single and multiple courses of radiotherapy to the spinal cord. METHODS A retrospective analysis was undertaken of all patients who were registered at the Princess Margaret Hospital between 1955 and 1985, and who developed permanent radiation myelopathy. There were 22 males and 13 females with ages ranging from 30 to 72 years. Twenty-four patients developed permanent myelopathy after one course of radiation therapy and 11 patients following retreatment. Seven patients had histological confirmation of radiation myelopathy at autopsy. RESULTS The actuarial survival was 14% at 5 years (median: 8.3 months) from the date of diagnosis of radiation myelopathy. Latent times for myelopathy following a single course of treatment (mean: 18.5 months, 7-57 months), were significantly longer than those after reirradiation (mean: 11.4 months, 4-25 months), p = 0.03. There was not a single incident of myelopathy in patients who received fractionated radiotherapy given once daily to an extrapolated response dose (ERD) of < or = 100 Gy2 (equivalent to 50 Gy in 25 daily fractions). Four patients who developed myelopathy after an ERD of < 100 Gy2 were all treated on accelerated fractionation protocols with multiple fractions given per day. Patients who were reirradiated received significantly higher doses (mean ERD of 148 Gy2) than those who had a single course of treatment (mean ERD of 121 Gy2), p = 0.001. CONCLUSIONS We conclude that the risk of radiation myelopathy following conventionally fractionated radiotherapy to the spinal cord is extremely small; giving multiple fractions per day reduces the spinal cord tolerance; latent time to myelopathy decreases following retreatment; and there is possible long-term recovery of radiation damage in the human spinal cord.