Two methods of assessment of baroreflex sensitivity were compared in eight supine healthy volunteers during repeated baseline measurements and various conditions of cardiac autonomic blockade. The spontaneous baroreflex method involved computer scanning of recordings of continuous finger arterial pressure and electrocardiogram to locate sequences of three or more beats in which pressure spontaneously increased or decreased, with parallel changes in pulse intervals. The mean regression slope of all these sequences during each study condition was considered to represent the mean spontaneous baroreflex slope. In the drug-induced method, sigmoidal curves were constructed from data obtained by bolus injections of phenylephrine and nitroprusside; the tangent taken at the resting pressure of each these curves were compared with the mean spontaneous baroreflex slopes. The two methods yielded slopes that were highly correlated (r=0.96, P<0.001), and significant but similar intra-individual baseline variability. Atropine virtually eliminated the baroreflex slope; subsequent addition of propranolol did not alter it further. Propranolol or clonidine alone increased average baroreflex slope to the extent that they increased resting pulse interval (r=0.69-0.83). The spontaneous baroreflex method provides a reliable, non-invasive assessment of human vagal cardiac baroreflex sensitivity within its physiological operating range.