In the past, muscle activation has been identified as having an important effect on the head-neck response in dynamic conditions. However, this claim has been largely based on global observations, and not by accurate analysis. In this study, the influence of muscle activation on the head-neck response is investigated by mathematical modeling. The detailed mathematical head-neck model presented by De Jager is improved by modeling the neck muscles in more detail. A multi-segment muscle description is applied in which the muscles curve around the vertebrae, resulting in realistic muscle lines of action. The model is validated with human volunteer responses to frontal and lateral impact at several severities. The model response with maximum muscle activation to high severity frontal and lateral impacts agrees well with volunteer responses, whereas a submaximum activation level or a larger reflex delay provides better results for the low severity impacts. The simulations show that muscle contraction has a large influence on the head-neck response.