Besides ethanol, acetic acid is produced in naturally fermenting sweet resources and is a significant environmental stress for fruit-breeding Drosophila populations and species. Although not related to the presence of an active alcohol dehydrogenase, adult acetic acid tolerance was found to correlate with ethanol tolerance when sensitive (Afrotropical) and resistant (European) natural populations of Drosophila melanogaster were compared. The same correlation was found when comparing various Drosophila species. Tolerance to acetic acid also correlated with the tolerance to longer aliphatic acids of three, four, or five carbons but did not correlate with the tolerance to inorganic acids (i.e., hydrochloric and sulfuric acids). These observations suggest that acetic acid is detoxified by the conversion of acetate into acetyl-CoA, a metabolic step also involved in ethanol detoxification. Future investigations on the adaptation of Drosophila to fermenting resources should consider selective effects of both ethanol and acetic acid.observations, little attention has been paid to the effects of acetic acid in Drosophila. Acetic acid has been shown to be used as a resource at low concentrations, whereas it is a stress at higher concentrations, and significant differences exist between species (11, 12). A recent article (9) stated that the genetics and physiology of adaptation ofD. melanogaster to acetic acid have yet to be studied.In the present study, we compared the acetic acid tolerances of two geographic populations of D. melanogaster, already known to differ markedly in their ethanol tolerances. Various species were also compared for their tolerance to both toxic agents. Toxicities of various other organic and inorganic acids were also studied, as well as the relationship between acetic acid tolerance and ADH activity. All results suggest that, although independent of ADH activity, acetic acid tolerance is a specific genetic trait related to the same metabolic pathway that allows ethanol detoxification.Most Drosophila species are saprophagous, and many of them that use decaying sweet substrates (e.g., fallen fruits) are faced with a large amount of ethanol, resulting from alcoholic fermentation of the resource (for reviews, see refs.