Sympathetic nerves play key roles in cardiac physiology and aging-related cardiovascular diseases. This study examined the effects of normal human aging on cardiac sympathetic innervation and function, including the neuronal uptake of catecholamines (uptake 1) via the cell membrane norepinephrine transporter. Thirty-three healthy volunteers, 17 under 40 and 16 over 50 y old, underwent thoracic PET scanning after injection of the sympathoneural imaging agent 6-¹⁸F-fluorodopamine. Myocardial perfusion was estimated by ¹³NH₃ scanning, and arterial blood was sampled for levels of 6-¹⁸F-fluorodopamine and 6-¹⁸F-fluorodopamine-derived radioactivity. The older group had more myocardial 6-¹⁸F-fluorodopamine-derived radioactivity than did the younger group. Myocardial perfusion was also greater in the older group, and arterial blood levels of 6-¹⁸F-fluorodopamine were also higher. After adjustment for delivery of the tracer, the estimated level of myocardial extraction of 6-¹⁸F-fluorodopamine was lower in the older group (48%) than in the younger group (74%) (P = 0.02). Cardiac uptake 1 activity decreases with normal human aging.