Gibbons (Hylobates lar) were used for the study of sequential dengue infections with the four dengue serotypes in an attempt to determine the extent of heterologous immunity conferred by infection. Thirty-three splenectomized young adult and six normal juvenile gibbons were infected with low-passage strains of each of the four dengue viruses in various sequences. It was found that in gibbons infected initially with dengue-2, 3, or 4 virus a second viremia developed after heterologous challenge with dengue-1, 2, or 4 virus but not with dengue-3 virus. In gibbons infected initially with dengue-1 virus no viremia developed on heterologous challenge, but all animals showed a significant increase in HI-antibody level after such challenge. In all instances gibbons were immune to homologous challenge. Third viremias could be induced regularly with a dengue-2-4-1 infection sequence. Neutralizing and HI antibodies to the challenge virus were present in all animals at the time of challenge. These antibodies were of low titer except for the gibbons infected initially with dengue-1 virus. No correlation was found between the antibody titer at the time of challenge and the development of a second viremia. No clinical signs that could be definitely attributed to the infection were noted in any of the infected gibbons.