Regular physical exercise is beneficial for both physical and mental health. By contrast, stress is associated with deleterious effects on health and there is growing evidence that regular physical exercise counteracts some of the effects of stress. However, most previous studies have suggested that prior exercise does not alter the acute hypothalamic pituitary adrenal (HPA) axis responses to stress. The present series of studies provides evidence that in rats, 6 weeks (but not 1 or 3 weeks) of voluntary wheel running reduces the HPA axis responses to lower-intensity stressors such as an i.p. saline injection, exposure to a novel environment or exposure to moderate intensity noise, but not to more intense stressors such as predator odour exposure or restraint. Daily exercise does not appear to be necessary for the reduction in HPA axis responses, with intermittent access (24 h out of each 72-h period) to a running wheel for 6 weeks, resulting in similar decrements in adrenocorticotrophic hormone and corticosterone release in response to 85 dBA noise exposure. Data from in situ hybridisation for c-fos mRNA are consistent with the hypothesis that voluntary exercise results in a decrease in HPA axis responsiveness to a low-intensity stressor at a central level, with no changes in primary sensory processing. Together, these data suggest that 6 weeks of daily or intermittent exercise constrains the HPA axis response to mild, but not more intense stressors, and that this regulation may be mediated at a central level beyond the primary sensory input.