Both mitral valve prolapse (MVP) and panic attacks have been reported to be associated with autonomic dysfunction, but previous studies have been limited by the lack of clear separation between patients with MVP and those with panic attacks and the use of noncomparable control subjects. Accordingly, heart rate and blood pressure responses to deep breathing, five minutes' quiet standing, and the Valsalva maneuver were studied in age- and cardiac symptom-matched groups of 33 control subjects, 66 patients with MVP, 20 patients with panic attacks, and 17 patients with both MVP and panic attacks. Compared with control subjects, patients with MVP exhibited more syncope (13 of 66, or 20 percent, versus none of 33, or 0 percent; p less than 0.01), more orthostatic hypotension during quiet standing (11 of 66, or 17 percent, versus one of 33, or 3 percent; p less than 0.01), loss of the normal decrease with age in vagally-mediated heart rate variability during deep breathing (r = 0.13, p = NS versus r = -0.44, p = 0.01), and lower 24-hour epinephrine excretion (6.1 +/- 0.7 versus 11.0 +/- 2.7 micrograms; p less than 0.01). In contrast, patients with panic attacks had greater increases than control subjects or patients with MVP without panic attacks in heart rate, mean blood pressure, and the product of heart rate and mean blood pressure during each minute of quiet standing and during the early strain phase of the Valsalva maneuver. These findings indicate that autonomic dysfunction occurs both in patients with MVP and in those with panic attacks in comparison with symptomatic control subjects, but that the patterns of abnormality differ. Patients with MVP exhibit decreased effectiveness of responses to orthostatic stress, reduced epinephrine excretion, and abnormal vagal tone, whereas patients with panic attacks have heightened cardiovascular responses to postural and positive intrathoracic pressure stresses.