The diaphragm, a ventilatory muscle, has abundant sensory innervation. The effects of phrenic afferent activation on ventilation have been varied. In this study the proximal end of the phrenic nerve was electrically stimulated, and the effects on ventilation were measured in supine dogs anesthetized with either alpha-chloralose or pentobarbital sodium. We found a maximum increase in ventilation of 45 +/- 4% in the alpha-chloralose group and an increase in mean arterial blood pressure of 18 +/- 4%. This response was obtained at high stimulus intensities (60 times twitch threshold). Stimulation of the proximal end of the gastrocnemius nerve produced a similar ventilatory response (61 +/- 10%) but at lower stimulus intensities. During pentobarbital sodium anesthesia both the hyperventilation and the pressor response were produced; however, ventilation was increased by an increase in respiratory frequency. The reflex was abolished by sectioning of the cervical dorsal roots (C4-C7). Proximal cold blockade of the nerve abolished the response at a perineural temperature of 1.35 +/- 0.64 degrees C. The main effect of activation of phrenic afferents was an increase in ventilation and blood pressure that was mediated by unmyelinated fibers and possibly thin myelinated fibers. This response is similar to skeletal muscle afferent activation and may play a role in ventilatory drive during such conditions as exercise and respiratory muscle fatigue.