The importance for fitness of epistatic interactions among mutations is poorly known, yet epistasis can exert important effects on the dynamics of evolving populations. We showed previously that epistatic interactions are common between pairs of random insertion mutations in the bacterium Escherichia coli. In this paper, we examine interactions between these mutations and other mutations by transducing each of twelve insertion mutations into two genetic backgrounds, one ancestral and the other having evolved in, and adapted to, a defined laboratory environment for 10,000 generations. To assess the effect of the mutation on fitness, we allowed each mutant to compete against its unmutated counterpart in that same environment. Overall, there was a strong positive correlation between the mutational effects on the two genetic backgrounds. Nonetheless, three of the twelve mutations had significantly different effects on the two backgrounds, indicating epistasis. There was no significant tendency for the mutations to be less harmful on the derived background. Thus, there is no evidence supporting the hypothesis that the derived bacteria had adapted, in part, by becoming buffered against the harmful effects of mutations.