The recent cloning of chicken genes coding for interleukins, chemokines, and other proteins involved in immune regulation and inflammation allowed us to analyze their expression during infection with Eimeria. The expression levels of different genes in jejunal and cecal RNA extracts isolated from uninfected chickens and chickens infected with Eimeria maxima or E. tenella were measured using a precise quantitative reverse transcription-PCR technique. Seven days after E. tenella infection, expression of the proinflammatory cytokine interleukin-1 (IL-1) mRNA was increased 80-fold. Among the chemokines analyzed, the CC chemokines K203 (200-fold) and macrophage inflammatory factor 1 (MIP-1) (80-fold) were strongly upregulated in the infected ceca, but the CXC chemokines IL-8 and K60 were not. However, the CXC chemokines were expressed at very high levels in uninfected cecal extracts. The levels of gamma interferon (IFN-␥) (300-fold), inducible nitric oxide synthase (iNOS) (200-fold), and myelomonocytic growth factor (MGF) (50-fold) were also highly upregulated during infection with E. tenella, whereas cyclooxygenase 2 showed a more modest (13-fold) increase. The genes upregulated during E. tenella infection were generally also upregulated during E. maxima infection but at a lower magnitude except for those encoding MIP-1 and MGF. For these two cytokines, no significant change in expression levels was observed after E. maxima infection. CD3؉ intraepithelial lymphocytes may participate in the IFN-␥ upregulation observed after infection, since both recruitment and upregulation of the IFN-␥ mRNA level were observed in the infected jejunal mucosa. Moreover, in the chicken macrophage cell line HD-11, CC chemokines, MGF, IL-1, and iNOS were inducible by IFN-␥, suggesting that macrophages may be one of the cell populations involved in the upregulation of these cytokines observed in vivo during infection with Eimeria.Chicken coccidiosis is caused by intracellular protozoan parasites belonging to seven species of Eimeria. These parasites invade and reside in the lining of the intestine or ceca. Parasite development causes diarrhea, morbidity, and mortality, and the impact of coccidiosis on the industry has serious economic consequences. Thus far, chemoprophylaxis has controlled the disease but has been complicated by the emergence of drug resistance. Infection by Eimeria promotes antibody and cellmediated immune responses. However, cellular immunity mediated by various cell populations, including T lymphocytes, NK cells, and macrophages, plays a major role in disease resistance (27). There is increasing evidence of CD4 ϩ and intraepithelial lymphocyte (IEL) involvement during a primary infection, while T-cell receptor ␣-and -chain-positive CD8 ϩ IEL play a key role in secondary infection (25). The development of a vaccine has been hampered by the lack of understanding of the various components of the host immune system involved in protective immunity.The low level of homology between chicken genes and their mammalian co...