The sensitivity of the rat spinal cord to single and split doses of radiation and the resulting relative biological effectiveness (RBE) were determined for carbon-ion irradiations (12C) in the plateau and Bragg-peak regions. The cranial part of the cervical and thoracic spinal cords of 180 rats were irradiated with one or two fractions of 12C ions or photons, respectively. Dose-response curves for the end point symptomatic myelopathy were established, and the resulting values for the ED50 (dose for 50% complication probability) were used to determine the RBEs. A median latency for myelopathy of 167 days (range, 121-288 days) was found. The ED50 values were 17.1 +/- 0.8 Gy, 24.9 +/- 0.7 Gy (one and two fractions, 12C plateau) and 13.9 +/- 0.8, 15.8 +/- 0.7 Gy (one and two fractions, 12C Bragg peak), respectively. For photons we obtained ED50 values of 24.5 +/- 0.8 Gy for single doses and 34.2 +/- 0.7 Gy when two fractions were applied. The corresponding RBEs were 1.43 +/- 0.08, 1.37 +/- 0.12 (one and two fractions, 12C plateau) and 1.76 +/- 0.05, 2.16 +/- 0.11 (one and two fractions, 12C Bragg peak), respectively. Hematoxylin and eosin staining revealed necrosis of the white matter in the spinal cord in all symptomatic animals. In summary, from one- and two-fraction photon, 12C plateau and Bragg-peak irradiation of the rat spinal cord, we have established RBEs as well as the individual ED50's. From the latter there is a clear indication of repair processes for fractionated photons and 12C plateau ions which are significantly reduced by using Bragg-peak ions. Additional studies are being carried with 6 and 18 fractions to further refine and define the RBE and ED50 values and estimate the alpha/beta ratios.