High-temperature origin-of-life theories require that the components of the first genetic material are stable. We therefore have measured the half-lives for the decomposition of the nucleobases. They have been found to be short on the geologic time scale. At 100°C, the growth temperatures of the hyperthermophiles, the half-lives are too short to allow for the adequate accumulation of these compounds (t 1/2 for A and G Ϸ 1 yr; U ؍ 12 yr; C ؍ 19 days). Therefore, unless the origin of life took place extremely rapidly (<100 yr), we conclude that a high-temperature origin of life may be possible, but it cannot involve adenine, uracil, guanine, or cytosine. The rates of hydrolysis at 100°C also suggest that an ocean-boiling asteroid impact would reset the prebiotic clock, requiring prebiotic synthetic processes to begin again. At 0°C, A, U, G, and T appear to be sufficiently stable (t 1/2 > 10 6 yr) to be involved in a low-temperature origin of life. However, the lack of stability of cytosine at 0°C (t 1/2 ؍ 17,000 yr) raises the possibility that the GC base pair may not have been used in the first genetic material unless life arose quickly (<10 6 yr) after a sterilization event. A two-letter code or an alternative base pair may have been used instead.A high-temperature origin of life (80°-110°C) is widely favored (1-6) because hyperthermophiles, which grow at temperatures between 80°and 110°C, are claimed to be the oldest organisms on the Earth (7), although there are dissenting opinions (8-11). Added support for this theory comes from atmospheric models depicting an early warm (Ϸ85°-110°C) Earth (12, 13). Models for an even higher temperature origin include proposals that life arose in the 350°C submarine vents (14-17) or between 150°and 250°C involving temperature and pH gradients (18).For a compound to be used in the first living organism it needs to be sufficiently stable so that the balance between synthesis and degradation does not result in vanishingly small concentrations. Previous studies have shown that a major problem with an origin of life between 250°-350°C is the stability of the presumed components of the first organisms, where the half-lives for decomposition are at most a few minutes (19)(20)(21)(22). These data, however, do not deal with an origin of life between 80°-110°C, where problems with the stability of RNA previously have been pointed out (23).We show here that the rapid rates of hydrolysis of the nucleobases A, U, G, C, and T at temperatures much above 0°C would present a major problem in the accumulation of these presumed essential compounds on the early Earth. A hightemperature origin of life involving these compounds therefore is unlikely. These results are applicable to any origin-oflife theory in which life begins with the evolution of a selfreplicating genetic system capable of undergoing Darwinian evolution. A high-temperature origin of life involving compounds other than those discussed here or involving the evolution of metabolic cycles before the evolution of the fi...