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Previously, we observed that serum from humans immune to dengue serotype 1 (dengue-1) neutralized the American genotype of dengue serotype 2 (American-2) to a greater ex- tent than it neutralized the Asian genotype of dengue serotype 2 (Asian-2). To determine if this activity is protective, Aotus nancymac monkeys were infected with dengue-1 followed by either American-2 or Asian-2. Dengue- 1-infected animals produced antibody with neutralizing titers of 2656 antibodies against dengue-1, 409 against American-2, and <20 against Asian-2. Infection with American-2 did not produce detectable viremia in either dengue-1-immune or den- gue-1-naive animals. These findings support the hypothesis that dengue- 1 immunity might have prevented disease or altered the severity of disease in individuals sequentially infected with dengue-1 and American-2. [ABSTRACT FROM AUTHOR]