Congenitally athymic nude (rnu/rnu) rats developed a high level of parasitemia and died with severe anemia after infection with Plasmodium berghei, while heterozygous littermates (rnu/+) showed a self-limiting infection and resisted further challenge. Transfer of normal thymocytes failed to protect rnu/rnu rats from the subsequent infection. Transfer of immune IgG fraction conferred resistance to malaria on rnu/+ but not on rnu/rnu rats. When both normal thymocyts and immune IgG were administered, rnu/rnu rats showed a self-limiting infection pattern, and a strong protective effect was demonstrated in the spleen after recovery. These results suggested that both T-cells and antibody were essential in developing protective immunity to malaria in this model.