Germfree (GF) and conventionally-reared (CV) mice were inoculated with a rodent blood parasite, Eperythrozoon coccoides. The parasitemia increased rapidly in GF and CV mice, and both groups of animals showed similar parasite levels 3 to 4 days after inoculation. The parasitemia started to decrease first in GF mice, but it was the CV group in which the parasitemia first became subpatent. Serum antibody to E. coccoides was first detected in CV mice, but eventually the magnitude of the antibody response was the same in both the GF and CV mice. The GF mice, however, revealed the greater immunoglobulin response in both IgM and 7Sγ globulins, whereas the CV mice manifested only an IgM response. The largest immunoglobulin response observed occurred in the 7Sγ2a and 7Sγ2b subclasses of CF mice. This study provided data on the serum antibody and immunoglobulin responses in GF and CV mice infected with E. coccoides. The inclusion of GF mice was invaluable because of the changes seen in 7Sγ globulin levels which were not observed in the CV group.