In sympathetic neurocirculatory failure (SNF), reflexive sympathetically mediated cardiovascular stimulation does not compensate for decreased cardiac filling. This explains orthostatic hypotension in chronic primary autonomic failure (CPAF). During phase 2 of the Valsalva maneuver (phase 2_L), blood pressure increases from its peak. During phase 4, blood pressure normally "overshoots" the baseline. Because these changes depend on sympathetically mediated cardiovascular stimulation, a progressive decrease in pressure during phase 2 and absence of the overshoot in phase 4 may indicate SNF. Moreover, because beat-to-beat blood pressure can be measured noninvasively using a photoplethysmographic or tonometric device, evaluating reflexive pressure responses might enable noninvasive diagnosis of SNF. This study assessed the relative frequencies of abnormal phase 2_L and phase 4 blood pressure in patients with CPAF and orthostatic hypotension and whether noninvasive measurement of beat-to-beat blood pressure can be used to diagnose SNF in patients. Twenty patients with chronic primary autonomic failure and orthostatic hypotension and 50 comparison patients, including several with CPAF but lacking orthostatic hypotension, underwent arterial pressure monitoring during performance of the Valsalva maneuver. Of the 20 patients with CPAF and orthostatic hypotension, all had an abnormal phase 2_L or phase 4 pressure response (sensitivity 100%), whereas only 3 of the 50 comparison patients had an abnormal response in either phase (specificity 94%). Seventeen patients with CPAF and orthostatic hypotension had abnormal responses in both phases (sensitivity 85%), but none of the comparison patients had such findings in both phases (specificity 100%). Of 13 patients in whom beat-to-beat blood pressure was recorded simultaneously invasively and noninvasively, all had abnormal blood pressure responses during phase 2_L and phase 4, whereas none of 29 comparison patients had such symptoms. Detection of abnormal blood pressure responses during phase 2_L or phase 4 of the Valsalva maneuver is a highly sensitive test for SNF. Abnormal pressure during these phases appears to identify SNF specifically. Noninvasive measurements can detect both of these abnormalities.