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.