Making predictions of the behavior of genetic networks may be even more complicatd than previously thought. Guet et al. (see the Perspective by Wigler and Mishra) created libraries of synthetic genetic networks in Escherichia coli. LacI, TetR, and lambda CI, along with five promoters regulated by these proteins, were linked together in various orders on plasmids. Two chemical inducers that change the binding state of LacI and TetR were used as inputs, and a fluorescent reporter of activity was used as the output. There were surprises even within such well-characterized components. A single swap of the connections between promoter and DNA-binding protein could dramatically change the behavior of the network.