Giant insects, with wingspans as large as 70 cm, ruled the Carboniferous and Permian skies. Gigantism has been linked to hyperoxic conditions because oxygen concentration is a key physiological control on body size, particularly in groups like flying insects that have high metabolic oxygen demands. Here we show, using a dataset of more than 10,500 fossil insect wing lengths, that size tracked atmospheric oxygen concentrations only for the first 150 Myr of insect evolution. The data are best explained by a model relating maximum size to atmospheric environmental oxygen concentration (pO 2 ) until the end of the Jurassic, and then at constant sizes, independent of oxygen fluctuations, during the Cretaceous and, at a smaller size, the Cenozoic. Maximum insect size decreased even as atmospheric pO 2 rose in the Early Cretaceous following the evolution and radiation of early birds, particularly as birds acquired adaptations that allowed more agile flight. A further decrease in maximum size during the Cenozoic may relate to the evolution of bats, the Cretaceous mass extinction, or further specialization of flying birds. The decoupling of insect size and atmospheric pO 2 coincident with the radiation of birds suggests that biotic interactions, such as predation and competition, superseded oxygen as the most important constraint on maximum body size of the largest insects.paleoecology | temperature | maximum likelihood estimation B ecause metabolic oxygen demand increases with increasing body size, environmental oxygen concentration (pO 2 ) is frequently invoked as an important constraint on the size of animals (1-6). Giant late Paleozoic insects, with wingspans as large as 70 cm, are the iconic example of the oxygen-body size link; hyperoxic conditions during the Carboniferous and Permian are thought to have permitted the spectacular sizes of the largest insects ever (2, 4). The physiological basis linking insect body size and pO 2 has been elucidated in numerous experimental tests (5,7,8). Body size and metabolic rate respond to pO 2 when insects are reared in hypoxic or hyperoxic atmospheres (7,8), although the effects are not uniform in all taxa (9). Flying insects should be particularly susceptible to variations in atmospheric pO 2 because their flight musculature has high energy demands (10), particularly during periods of active flight (11, 12). The volume occupied by tracheae, tubes that transport oxygen throughout the body, scales hypermetrically with body volume, imposing further surface area-to-volume constraints on maximum size (13,14).Although these responses underscore the physiological importance of oxygen, developmental plasticity exhibited by different insect groups may not be indicative of evolutionary changes (15), especially in natural settings where other abiotic influences, biotic interactions, and selective pressure from allometric scaling of life-history traits are also important (16)(17)(18)(19)(20). For example, temperature can also be an important influence on insect body size via physiologica...