When normal-lived Ra strain Drosophila were indirectly selected for longevity, they gave rise to long-lived La strain animals with lower oxidized protein and lipid levels that were temporally coincident with higher antioxidant activities. We wanted to determine whether it was possible to create long-lived animals by a direct selection for increased antioxidant activities. Using the same Ra strain, we selected them over 24 generations for increased resistance to paraquat. Selection was successful: the paraquat-resistant flies had a fourfold increase in their LT(50) (mean lethal time) values. Their extended longevity pattern differs from that of the La strain. The paraquat-resistant animals also have a lower level of antioxidant activity, an increased total P450 enzyme activity level, an altered pattern of energy metabolism, and a significantly lower developmental viability. We interpret these findings as suggesting that similar stress response phenotypes may be generated by different molecular mechanisms, some of which may generate very different types of extended longevity phenotypes.