The aim of this study was to determine whether shorter-lived radionuclides can reduce red marrow (RM) toxicity for i.p. radioimmunotherapy (RIT). The potential radionuclides, which included Lu-177, I-131, Y-90, Re-186, Re-188, and Ho-166, were attached to antibody CC49. Each radiopharmaceutical was assumed to have identical in vivo pharmacokinetics. Blood and whole body retention data acquired from 26 patients who received i.p. RIT with Lu-177 CC49 were used as input. The average biological half-time of Lu-177 CC49 in the whole body was 280 h, and the average Lu-177 concentration in plasma increased to a maximum at 2 days postinfusion, followed by steady clearance. The residence time and RM doses were calculated for each radionuclide. In the current model, Re-188 was found to deliver the lowest RM dose, primarily because it had the shortest half-life, whereas Y-90 delivers the highest dose. Re-188 delivers 60% of the RM dose as compared with Lu-177 and can increase the dose to metastatic sites in the i.p. space by a similar factor. Based on limiting the RM dose to 200 cGy, the maximum administered activity of each radionuclide is as follows: (a) 106 mCi, Lu-177; (b) 58 mCi, I-131; (c) 34 mCi, Y-90; (d) 70 mCi, Re-186; (e) 169 mCi, Re-188; and (f) 110 mCi, Ho-166. Because of the delayed steady leakage of radiopharmaceuticals from the i.p. cavity to the plasma, short-lived radionuclides may offer special advantages for i.p. RIT.