Methods and devices for selectively removing an agent from a physiological efferent fluid collection site are provided. A feature of the invention is that a non-occlusive aspiration device is employed to selectively remove the target agent from the site only when the target agent is present in the site. Also provided are systems and kits for performing the subject methods. The subject invention finds use in a variety of different applications, including the selective removal of both therapeutic and diagnostic agents from a variety of different physiological sites.