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Three forms of immunosuppression (splenectomy, antilymphocyte serum [ALS], and hydrocortisone) were studied in mice infected intraperitoneally with Plasmodium berghei yoelii (2 × 106 parasitized erythrocytes). Splenectomy, performed 10 days before infection, impaired antibody synthesis and converted this self-limited infection to a 100% lethal infection. Antibody was measured by the indirect fluorescent-antibody (IFA) test. ALS (0.3 ml intraperitoneally every 3 days starting 6 days before infection and continuing through the infection) and hydrocortisone (4 mg intraperitoneally daily starting 1 day before infection and continuing through the infection) also impaired both antibody synthesis and recovery, but most mice eventually overcame the infection. In survivors, the appearance of antibody coincided with a decrease in parasitemia, suggesting that a humoral immunity is one of the factors essential to recovery from this malaria.