In many regions of the world, including sub-Saharan Africa, concomitant infection with multiple parasites is common. In order to examine the effects of filariasis, a chronic helminth infection, on immune responses and clinical manifestations of acute malaria infection, the authors followed 31 filaria-infected (FIL+) and 31 filaria-uninfected (FIL–) individuals living in a malaria-endemic area of Mali through an entire malaria transmission season for the development of clinical malaria (fever or other symptoms of malaria in the setting of detectable blood parasites). Serum levels of inflammatory cytokines previously associated with severe malaria were decreased in FIL+ subjects at the time of acute clinical malaria. Although there were no differences between FIL+ and FIL– subjects with respect to the time of first episode of malaria or the number or severity of malaria episodes, filarial infection appeared to protect against the development of anemia during the malaria transmission season. These findings demonstrate that chronic filarial infection modulates the immune response to acute malaria. The apparent effect on anemia is intriguing and deserves further study.