Stress is a well-known factor affecting cardiac contractility through the cardiac sympathetic nerves. A positive inotropic effect of the cardiac sympathetic nerves on the myocardium is reflected by pre-ejection period (PEP) shortening. Patients with Parkinson disease (PD) and neurogenic orthostatic hypotension (NOH) (PD + NOH) or with pure autonomic failure (PAF) have markedly decreased myocardial 6-[18F]Fluorodopamine-derived radioactivity, reflecting cardiac sympathetic denervation. The functional effects of the cardiac sympathetic denervation have been unknown. We measured PEP and heart rate-corrected PEP (PEPI) responses to i.v. tyramine (1 mg/min) in 13 patients (9 PD + NOH and 4 PAF) with low 6-[18F]Fluorodopamine-derived radioactivity and in subjects with normal radioactivity (15 multiple system atrophy with NOS patients (MSA + NOS). Baseline PEP and PEPI did not differ between the groups. By 10 min after initiation of tyramine infusion, PEP and PEPI were significantly lower (P < 0.01) in MSA + NOS, compared to base line, whereas PEP and PEPI remained unchanged in the PD + NOH/PAF group. The PEP and PEPI decrease was larger in the MSA + NOS group than in the PD + NOH/PAF group (P < 0.05). One of the functional consequences of cardiac sympathetic denervation is failure to increase contractility in response to stimuli that depend on endogenous norepinephrine release.