The goal of part II of this study was to evaluate functional characteristics of leukocytes and circulating blood cell parameters after whole-body proton irradiation at varying doses and at low- and high-dose-rates (LDR and HDR, respectively). C57BL/6 mice (n=51) were irradiated and euthanized at 4 days post-exposure for assay. Significant radiation dose- (but not dose-rate-) dependent decreases were observed in splenocyte responses to T and B cell mitogens when compared to sham-irradiated controls (P<0.001). Spontaneous blastogenesis, also significantly dose-dependent, was increased in both blood and spleen (P<0.001). Red blood cell counts, hemoglobin concentration, and hematocrit were decreased in a dose-dependent manner (P<0.05), whereas thrombocyte numbers were only slightly affected. Comparison of proton- and gamma-irradiated groups (both receiving 3 Gy at HDR) showed a higher level of spontaneous blastogenesis in blood leukocytes and a lower splenocyte response to concanavalin A following proton irradiation (P<0.05). There were no dose rate effects. Collectively, the data demonstrate that the measurements in blood and spleen were largely dependent upon the total dose of proton radiation and that an 80-fold difference in the dose rate was not a significant factor. A difference, however, was found between protons and gamma-rays in the degree of change induced in some of the measurements.