BACKGROUND Upright posture intolerance can be seen in a variety of diseases but the current methodology is not quantifiable and limits the ability to identify response to treatment. METHODS A standard questionnaire was developed to assess the following aspects of upright posture tolerance: (1) How long can you stand straight without any support? (2) Do you feel any sense of sickness when you sit or lie down after standing? (3) How long do you have to wait before you are comfortable standing again after you have stood straight? (4) How effectively and fast can you get up from sitting or lying position to stand straight? and (5) rate the ability to perform activities on a standard vertical visual analog scale between 100 (can do everything) and 0 (cannot do anything). We tested the ability of the questionnaire in four patients to identify various aspects of upright posture intolerance. RESULTS The questionnaire was administered to four patients who reported upright posture intolerance. The patients with either intracranial hypotension syndrome, postural hypotension, or Klippel-Feil syndrome reported less than optimal performance in four of five components of the questionnaire. The patient with vertebrobasilar ischemia reported less than optimal performance in two of five components. CONCLUSIONS A new questionnaire is developed for self-administration to identify various components of upright posture intolerance and detect response to treatment.