Many lines of experimental evidence suggest the interplay of the autonomic nervous system and a variety of mediators of vascular atheroma and ultimately vascular occlusion. In vivo study in human volunteers and patients is hampered by the lack of a reliable and sensitive marker of prevailing autonomic tone able to reflect the appropriate dynamic change in nervous activity. Currently, the modern standard for definition of autonomic tone is based on a variety of analyses of R-R interval variability from the surface ECG. In this review, we consider whether heart rate variability techniques are sensitive enough to define relevant clinical interactions between neural tone and other mediators of vascular occlusion--specifically, mechanical pressure, thrombotic and hormonal factors--which are relevant to atherosclerotic vascular disease.