Low dose total body irradiation (TBI) administered in small fractional doses (5-10 cGy) for the treatment of disseminated malignancies such as chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma can be extremely toxic with substantial bone marrow depression. We elected to study bone marrow suppression following fractionated TBI in the rabbit. New Zealand white/female rabbits were thus treated with one of the following three schedules: (1) 3 fractions of 10 cGy per week; (2) 5 fractions of 10 cGy per week; and (3) 5 fractions of 25 cGy per week. Total doses ranged from 1050 to 2625 cGy and animals were sacrificed immediately, 4 weeks, or 8 weeks following completion of therapy. With the 10 cGy/day schedules, slight depression of total WBC counts and lymphocyte numbers occurred during and to the completion of irradiation followed by a rebound to greater than normal levels. With the 25 cGy schedule, a significant WBC and lymphocyte depression occurred at an accumulated dose of 1000 cGy and continued to decrease up to 2500 cGy, followed again by a rebound to greater than normal levels. The depression with the 25 cGy fractions was significantly greater than with the 10 cGy daily fractions. Thus, the severe and persistent peripheral blood count depression observed in CLL patients treated with TBI in small fractional doses was not reproduced in the normal rabbits. Possible explanations for this paradox are offered.