SIV rats infected with a high dose (50000 oocysts) of Eimeria nieschulzi displayed clinical symptoms of coccidiosis such as diarrhoea (days 6 and 7 post-primary infection) and weight loss (days 6–8 post-primary infection) and were completely immune to challenge with a similar dose. The ability of rats to produce tumour necrosis factor (TNF) in vivo was enhanced during the period of oocyst excretion in the primary infection but significant production of TNF did not occur after challenge infection. Thus, TNF does not appear to be an important factor in resistance to infection with E. nieschulzi but may play some role in resistance to primary infection and in the pathology associated with E. nieschulzi infection. Parasite-specific serum IgM levels (measured by enzyme-linked immunosorbent assay) were also increased during primary infection but returned to background levels at the end of the patent period and were not affected by challenge infection. In contrast to TNF and IgM, serum concentrations of E. nieschulzi-specific IgGl, IgG2a, IgG2b, IgG2c and intestinal tissue levels of IgA did not begin to increase until after day 12 post-primary infection, reached peak levels between days 20 and 30 post-primary infection and were slightly increased by challenge infection.