Abstract Gene interactions are emerging as central to understanding the realization of any phenotype. To probe the flexibility of interactions in a defined gene network, we isolated a set of 16 interacting genes in Drosophila, on the basis of their alteration of a quantitative behavioral phenotype—the loss of coordination in a temperature-sensitive allele of Syntaxin1A. The interactions inter se of this set of genes were then assayed in the presence and in the absence of the original Syntaxin1A mutation to ask whether the relationships among the 16 genes remain stable or differ after a change in genetic context. The pattern of epistatic interactions that occurs within this set of variants is dramatically altered in the two different genetic contexts. The results imply considerable flexibility in the network interactions of genes.