O bstructive lung disease is the most common form of respiratory disturbance. However, the location of brain structures underlying the ventilatory response to resistive expiratory loads is unknown in humans. To study this issue, midsagittal magnetic resonance images were acquired in eight healthy volunteers before and after application of a moderate resistive expiratory load (30 cmH2O/liter/s), using functional magnetic resonance imaging (fMRI) strategies (1.5-T magnetic resonance; repetition time: 72 ms; echo time: 45 ms; flip angle: 30 degrees; field of view: 26 cm; slice thickness: 5 mm; 128 x 256 x 1 number of excitations). Digital image subtractions and region of interest analyses revealed significant increases in fMRI signal intensity in discrete areas of the ventral medulla, ventral and dorsal pontomedullary structures, basal forebrain, and cerebellum. Upon load withdrawal, a rapid fMRI signal off-transient occurred in all activated sites. Application of an identical load immediately after recovery from the initial stimulus resulted in smaller signal increases (P < 0.02). Prolongation of load duration was associated with progressive fMRI signal decrease across activated regions. In three additional subjects, the threshold for significant MRI signal increases was established at expiratory loads > or = 15 cmH2O/liter/s and was dose dependent with increasing loads. We conclude that resistive expiratory loads > or = 15 cmH2O/liter/s elicit regional activation of discrete brain locations in humans.