In addition to its natriuretic, hormonal and vascular actions, atrial natriuretic factor (ANF) may interact importantly with the function of the autonomic nervous system. It has been hypothesized that ANF may exert its cardiovascular and possibly renal effects by interfering with autonomic control mechanisms. In, animal experiments the hypotension that is caused by ANF is usually not associated with the expected reflex tachycardia or increased efferent sympathetic activity. Furthermore, bilateral vagotomy can attenuate the hypotensive action of ANF which suggest that ANF may stimulate sympathoinhibitory afferent vagal activity from the cardiopulmonary baroreceptor system. In man, ANF may alter reflexogenic-mediated forearm vascular responses to cardiopulmonary deactivation which suggest that ANF may have an important role as a neuromodulator of autonomic nervous function, a role that could serve to amplify or facilitate the peripheral hormonal actions of ANF. This neuromodulating influence of ANF could be due to several mechanisms: it could modulate baroreflex mechanisms or it could have direct effects on autonomic centres in the brain or it could have effects on peripheral neurotransmission. The role of the autonomic nervous system in modulating the release of ANF remains controversial. Finally, there is growing evidence to suggest that there is a reciprocal interplay between ANF and the sympathetic nervous system in peripheral target tissues which may have important pathophysiological significance.