The antibody responses of rats to infection with the intestinal intracellular protozoan parasite Eimeria nieschulzi were examined by a sensitive radio-immunoassay with a soluble preparation of sporulated oocysts as antigen. Specific antibodies of the IgM, IgG1, IgG2a and IgG2b isotypes were found in the blood circulation and IgA antibodies were detected in the bile and in intestinal washings. The IgM response was rapid, its peak was relatively brief and it was not recalled by the reinoculation of oocysts. There were some differences between the responses in the different subclasses of IgG but they all reached a peak between 20-30 days after the initiation of the primary infection and there was an anamnestic response to a challenge inoculation of oocysts. IgA antibodies to E. nieschulzi antigen in the bile and in intestinal washings increased and decreased after both primary and secondary inocula. Antibodies of all isotypes tested were virtually absent in the blood circulation of infected athymic rats. These findings are discussed with reference to antibody responses to other parasitic infections and to the role of antibodies in immunity to coccidiosis.