Transcription of the thrU(tufB) operon is trans-activated by the protein FIS which binds to the promoter upstream activator sequence (UAS). Deletions of parts of the UAS and insertions show that optimal transactivation requires occupation by FIS of the two FIS-binding regions on the UAS and specific helical positioning of these regions. On the basis of these and other data, a model for the mechanism of thrU(tufB) trans-activation by FIS is proposed. This model implies that the mechanisms underlying stimulation by FIS of two totally different processes: inversion of viral DNA segments and transcription of stable RNA operons, are essentially the same.