Host-parasite interactions during coccidial infection are complex, and host responses leading to parasite elimination are not well understood. Interactions between host cells and parasites were investigated using two-color immunofluorescent staining of duodenal tissue infected withs Eimeria acervulina. Tissues were removed from TK strain chickens 24, 48, and 72 h after primary infection with 2.5 × 107 normal or irradiated oocysts and also following secondary infection with 2.5 × 107 normal oocysts. The tissues were embedded in freezing compound, frozen, sectioned, and fixed in cold acetone. Sections were stained with monoclonal antibodies to identify CD4+, CD8+, Ig+, and Bu1a+ lymphocytes, as well as macrophages and parasites. At 24 h after all infections, sporozoites were seen primarily in CD8+ lymphocytes and macrophages. Many CD8+ lymphocytes were seen at all times in infected tissues and frequently appeared to be in contact with infected epithelial cells. Sporozoites were occasionally seen in CD4+ lymphocytes but none were noted in Ig+ or Bu1a+ lymphocytes. Meront development was extensive after primary infection with normal oocysts, sparse after primary infection with irradiated oocysts, and moderate after secondary infection.