Previous studies indicated that renal tubular epithelial cells from some long-lived avian species exhibit robust and/or unique protective mechanisms against oxidative stress relative to murine cells. Here we extend these studies to investigate the response of primary embryonic fibroblast-like cells to oxidative challenge in long- and short-lived avian species (budgerigar, Melopsittacus undulatus, longevity up to 20 years, vs Japanese quail, Coturnix coturnix japonica, longevity up to 5 years) and short- and long-lived mammalian species (house mouse, Mus musculus, longevity up to 4 years vs humans, Homo sapiens, longevity up to 122 years). Under the conditions of our assay, the oxidative-damage resistance phenotype appears to be associated with exceptional longevity in avian species, but not in mammals. Furthermore, the extreme oxidative damage resistance phenotype observed in a long-lived bird requires active gene transcription and translation, suggesting that specific gene products may have evolved in long-lived birds to facilitate resistance to oxidative stress.