Systemic arterial baroreceptors located in the carotid sinus, right subclavian-brachiocephalic angle, and aortic arch are well known for their important regulatory effects on cardiovascular, renal, and ventilatory functions. Although it has been assumed that baroreflex responses result from the stimulation of baroreceptors with myelinated afferent fibers (A-fibers), it has become clear in recent years that another type of baroreceptor with nonmyelinated afferent fibers (C-fibers) exists and may contribute to baroreflexes. In addition, a second group of arterial C-fiber endings (chemosensitive endings) have been found which are of interest not only for their response to pressure, but also for their response to endogenous substances such as bradykinin and prostaglandins that may play a role in circulatory adjustments. The functional importance of C-fiber baroreceptors and chemosensitive endings is not yet known. A systematic study of the distribution, afferent properties, and reflex functions of these arterial C-fibers in the carotid sinus, right subclavian angle, and aortic arch will be performed in anesthetized dogs in which the vasosensory regions will be vascularly isolated and distended with controlled pressures. The distribution of C-fiber baroreceptors and chemosensitive endings and their afferent responses to changes in arterial pressure, to short term hypertensive resetting, to changes in firing of sympathetic nerves supplying the baroreceptor area, and to endogenous chemical substances (catecholamines, bradykinin, prostaglandins) will be determined by recording impulses from single nerve fibers in each of the vasosensory regions. The reflex effects of arterial C-fibers will be determined by stimulating baroreceptors in response to increased pressure or chemosensitive endings in response to administration of chemicals when afferent A-fibers are blocked selectively by cooling the appropriate vasosensory nerve. These studies will define reflex effects on heart rate, cardiac output, arterial pressure, vascular resistance, renal nerve activity, plasma vasopressin concentration and renin activity, minute ventilation, and airway resistance. By elucidating both the conditions in which arterial C-fibers are stimulated and their reflex effects, these studies will provide insights into the functional importance of C-fiber baroreceptors and chemosensitive endings in the reflex regulation of the heart, peripheral circulation, kidney, and respiratory system under a variety of physiological and pathophysiological conditions.