The aim of the study was the characterization of the local immune response of Lewis rats to Eimeria separata, a caecum-dwelling coccidium. Rats infected twice at 10-day intervals with 5,000 oocysts developed a high degree of immunity to a heavy challenge with 100,000 oocysts, reducing the oocyst production by > 98% when compared with naive recipients. Histopathological investigations performed over a period of 0-72 h post-infection (pi) showed that 1st generation schizonts, developed within 24 h pi, represented the major target stages, although later stages were also affected. Preinfected animals showed significantly more lymphocytes in the caecum wall than naive animals. An increase in lymphocyte numbers after challenge observed in both groups was enhanced in challenged animals up to 36 h pi. The number of lamina propria lymphocytes predominantly was increased after primary infection whereas in repeatedly infected animals the increase also concerned intraepithelial lymphocytes. In addition, the numbers of plasma cells were enhanced in the caecum wall of immune animals. Macrophage infiltration in the caecum wall followed a similar time course in both groups up to 36 h pi. A subsequent further rise up to 48 h pi was enhanced in naive rats. Tissue infiltrations with eosinophils and mast cells were observed predominantly in the repeatedly infected rats. No obvious changes occurred with intestinal neutrophils and goblet cells. In conclusion, caecum tissue alterations suggest an early local immune response, which is related to development and maturation of the parasite.