We present a kinetic model for the sequence-dependent motion of RNA polymerase (RNAP) during transcription elongation. For each NTP incorporation, RNAP has a net forward translocation of one base-pair along the DNA template. However, this process may involve the exploration of back-tracked and forward-tracked translocation modes. In our model, the kinetic rates for the reaction pathway, calculated based on the stabilities of the transcription elongation complex (TEC), necessarily lead to sequence-dependent NTP incorporation rates. Simulated RNAP elongation kinetics is in good agreement with data from transcription gels and single-molecule studies. The model provides a kinetic explanation for well-known back-tracked pauses at transcript positions with unstable TECs. It also predicts a new type of pause caused by an energetically unfavorable transition from pre to post-translocation modes. © 2004 Elsevier Ltd. All rights reserved.