The function and course of the cortico-respiratory projections in man are not yet well established. In 30 normal volunteers respiratory muscles were activated by magnetic stimulation of the motor cortex and the cervical and thoracic spinal roots with bilateral recordings from the respiratory muscles. Following cortical stimulation contralateral responses were obtained in all subjects during voluntary inspiration showing a mean latency and amplitude of 13.4+/-1.4ms/1.6+/-1.2 mV (stimulation of the left hemisphere) and 13.2+/-1.3ms/2.5+/-2.5 mV (stimulation of the right hemisphere). Ipsilateral responses were obtained in only 18 (right side) and 21 (left side) subjects and had a significantly (p < 0.001) longer mean latency and lower mean amplitude than the contralateral responses. In 31 patients with impairment of the cortico-respiratory projections due to cerebral infarction demonstrated by magnetic resonance imaging studies, the responsible lesion topography was analysed. We found that, 1. the voluntary activation of respiratory muscles is mediated predominantly by the contralateral motor cortex, 2. the descending cortico-respiratory projections are located within the pyramidal tract, and 3. the cortico-respiratory projections to the respiratory muscles are frequently affected in patients with hemiparesis due to acute stroke. These findings might explain the increased incidence of pneumonia at the hemiparetic side in patients with cerebral ischemia as shown in previous studies.