Anemia has long been reported to adversely affect the efficacy of radiation treatment in cervical cancer. On the basis of these findings, many radiation oncologists routinely use blood transfusions with the intent to maintain hemoglobin above specified levels during radiation therapy. However, allogeneic blood transfusions have been previously linked with biological and clinical phenomena correlated with immune suppression. In this study we have analyzed the effects of blood transfusion on the outcome of 130 patients with stage-IIB and -III cervical carcinomas treated with external radiation and intracavitary brachytherapy with or without concomitant platinum administration at the University of Arkansas for Medical Sciences between 1990 and 1999. With the exception of hemoglobin and hematocrit levels at the onset of treatment between the transfused and untransfused groups (p < 0.001), the distribution of age, histology, total radiation dose and duration of treatment were not significantly different between the 2 groups of stage-IIB and -III patients. Among the 45 stage-IIB patients who received blood during radiation treatment, there were 31 deaths (68.8%), compared with 14 (31.8%) among the 44 patients who did not receive blood (p > 0.05). Among the 30 stage-III patients who received blood during radiation treatment, there were 27 deaths (90%), compared with 6 (54%) among the 11 patients who did not receive blood (p > 0.11). In multivariate analysis of survival, there was a significant difference due to transfusion with a risk ratio (RR) of 2.6 (95% CI 1.6, 4.2; p < 0.001) after adjusting for no chemotherapy (RR = 2.2, 95% CI 1.4, 3.5; p < 0.001), considering all patients collectively, stage-IIB patients only (RR = 1.9, 95% CI 1.1, 3.3; p < 0.01), and stage-III patients only (RR = 3.2, 95% CI 1.2, 8.7; p < 0.02). These results suggest that routine blood transfusion of anemic cervical cancer patients does not improve outcome and may represent an independent variable predictive of diminished survival during primary radiation treatment for cervical cancer. Prospective randomized studies are strongly warranted to confirm this hypothesis.