Macrophages are potent elicitors of inflammatory reactions that can play both positive and negative roles in radiotherapy. While several studies have investigated the effects of X-rays or gamma-rays on macrophages, virtually no work has been done on the responses of these cells to irradiation with carbon ions. Investigations into the effects of carbon ion irradiation are of particular interest in light of the fact that this type of radiation is being used increasingly for cancer therapy. In the present investigation we compared the effects of 250 kV X-rays with those of 9.8 MeV/u carbon ions on RAW 264.7 macrophages over a wide range of radiation doses. Macrophage functions including vitality, phagocytic activity, production of the proinflammatory cytokines IL-1β and TNFα and production of nitric oxide (NO) were measured. In comparison to lymphocytes and fibroblasts, macrophages showed only a small decrease in vitality after irradiation with either X-rays or carbon ions. Proinflammatory cytokines and NO were induced in macrophages by LPS but not by irradiation alone. X-rays or carbon ions had little modulating effect on LPS-induced TNFα production. However, LPS-induced NO increased in a dose dependent manner up to 6-fold after carbon ion irradiation, while X-ray irradiation did not have this effect. Carbon ion irradiation mediated a concomitant decrease in IL-1β production. Carbon ions also had a greater effect than X-rays in enhancing the phagocytic activity of macrophages. These results underscore the greater potential of carbon ion irradiation with regard to radiobiological effectiveness.