Bacillus calmette-guérin (BCG)-vaccination raised dramatically the survival rates of A/J mice from infection by Plasmodium yoelii 17XL at blood-stage. The analysis of the immune response of spleen cells indicated that BCG vaccination biased the immune response toward Th1 type. Neutralization of IFN-gamma and nitric oxide abrogated the protection. The kinetics of Ab production in the course of P. yoelii 17XL infection was monitored. Surprisingly, larger amounts of parasite-specific Abs were produced in BCG-vaccinated mice than in the placebo control. The vast majority of the produced IgG against parasites in BCG-vaccinated mice was IgG2a, which was observed hardly in placebo controls. The peak of IgG2a production coincided with the clearance of infection. The naive mice transferred adoptively with IgG2a from self-cured mice survived the lethal challenge from the parasite. These data indicated that BCG vaccination protected A/J mouse from P. yoelii 17XL infection by biasing immunity toward Th1-type after parasite infection and enhancing production of IgG2a, which ultimately played a major role in protection.