Acidic and basic fibroblast growth factors (FGF(1/2)) myeloprotect mice in single dose total body irradiation (TBI) experiments with a dose modification factor (DMF) of approximately 1.15. CFU-C assay suggests that one of the mechanisms is augmentation of the shoulder of the radiation dose response curve, and thus protection could be greater with fractionation. Four equal fractions of TBI were delivered to C3H/He mice at times 0 h, 8 h, 24 h, and 32 h. FGF(1/2) dose was 3 microg per i.v. injection given 24 and 4 hrs before the first radiation dose. FGF2 treated mice had a significant survival advantage over saline-treated mice with a DMF of 1.22 +/- 0.07 (p < 0.01). Adding a third dose of FGF2, had no additional benefit on LD(50/30) (dose of radiation lethal to 50% of animals measured at day 30) (DMF = 1.23 +/- 0.06, p < 0.01). FGF1 was not as effective with fractionation (DMF = 1.04 +/- 0.03). Increased survival in FGF2 treated mice was due to the a more rapid recovery of bone marrow hematopoietic cells and peripheral WBC, RBC and platelets. FGF2 may prove a useful treatment response modifier in clinical fractionated irradiation.