Most natural environments experience fluctuating temperatures that acutely affect an organism's physiology and ultimately a species' biogeographic distribution. Here we examine whether oxygen delivery to tissues becomes limiting as body temperature increases and eventually causes death at upper lethal temperatures. Because of the limited direct, experimental evidence supporting this possibility in terrestrial arthropods, we explored the effect of ambient oxygen availability on the thermotolerance of insects representing six species (Acheta domesticus, Hippodamia convergens, Gromphadorhina portentosa, Pogonomyrmex occidentalis, Tenebrio molitor, and Zophobus morio), four taxonomic orders (Blattodea, Coleoptera, Hymenoptera, and Orthoptera), and multiple life stages (e.g., adults vs. larvae or nymphs). The survival curves of insects exposed to temperatures (45° or 50°C) under normoxic conditions (21% O(2)) were compared with those measured under altered oxygen levels (0%, 10%, 35%, and 95% O(2)). Kaplan-Meier log rank analyses followed by Holm-Sidak pairwise comparisons revealed that (1) anoxia sharply diminished survival times in all groups studied, (2) thermotolerance under moderate hyperoxia (35% O(2)) or moderate hypoxia (10% O(2)) was the same as or lower than that under normoxia, (3) half of the experimental treatments involving extreme hyperoxia (95% O(2)) caused reduced thermotolerance, and (4) thermotolerance differed with developmental stage. Adult G. portentosa exhibited much higher thermotolerance than their first-instar nymphs, but responses from larval and adult Z. morio were equivocal. We conclude that some factor(s) separate from oxygen delivery is responsible for death of insects at upper lethal temperatures.