Plasmodium berghei (NYU-2 strain), a virulent rodent malarial parasite, was used to infect germfree (GF) and conventionally-reared (CV) mice. The parasitemia increased more rapidly in CV mice, and maximum parasite levels occurred 6 days after inoculation. Maximum parasitemia was reached 10 days after inoculation in GF mice, and the parasite levels were approximately the same as observed in CV mice at peak parasitemia. Serum antibody was detected earlier, and the overall antibody response was greater in GF mice than in the CV group. A greater immunoglobulin response was observed in GF mice. Most noticeable was the rapid and continuous increase in 7Sγ2b levels throughout the course of infection, whereas no significant changes in 7Sγ2b levels were detected in the CV group. In spite of the serum antibody and immunoglobulin responses elicited, these were not adequate for protection because all mice died as a result of the P. berghei infection.