Pulmonary C-fibers initiate the prompt apnea evoked by pulmonary arterial injections of capsaicin, but their role in the subsequent rapid shallow breathing of the pulmonary chemoreflex is disputed. To determine whether this reflex tachypnea is triggered by pulmonary C-fibers rather than by afferents further downstream, we separately perfused the pulmonary and systemic circulation in anesthetized dogs. When the lungs were rhythmically inflated, injection of capsaicin (0.5-20.0 micrograms X kg-1) into the isolated pulmonary circulation evoked an immediate cessation of phrenic nerve firing ("apnea") and when phrenic bursts resumed, a reduction in their amplitude. Phrenic burst frequency was usually entrained to the ventilator cycle and did not increase. By contrast, when entrainment of phrenic bursts was avoided by statically inflating the lungs at a transpulmonary pressure of 3 cmH2O, the injection of capsaicin evoked apnea, followed by a prolonged increase in phrenic burst frequency and a decrease in amplitude ("rapid shallow breathing"). The infusion of capsaicin (10-20 micrograms X kg-1 X min-1) also evoked rapid shallow breathing, but without apnea. Our results are consistent with the hypothesis that in spontaneously breathing animals, stimulation of pulmonary C-fibers evokes rapid shallow breathing.