Changes in the subject's breathing rate or depth, such as a breath-hold challenge, can cause significant MRI signal changes. However, the response function that best models breath-holding-induced signal changes, as well as those resulting from a wider range of breathing variations including those occurring during rest, has not yet been determined. Respiration related signal changes appear to be slower than neuronally induced BOLD signal changes and are not modeled accurately using the typical hemodynamic response functions used in fMRI. In this study, we derive a new response function to model the average MRI signal changes induced by variations in the respiration volume (breath-to-breath changes in the respiration depth and rate). This was done by averaging the response to a series of single deep breaths performed once every 40 s amongst otherwise constant breathing. The new "respiration response function" consists of an early overshoot followed by a later undershoot (peaking at approximately 16 s), and accurately models the MRI signal changes resulting from breath-holding as well as cued depth and rate changes.