Orthostatic hypotension in human immunodeficiency virus infection may be the result of generalized autonomic nervous system dysfunction. We used an autonomic nervous system (ANS) testing battery to determine if generalized ANS dysfunction was present in five human immunodeficiency virus-positive (HIV+) patients presenting with severe orthostatic hypotension (OH). All five patients had abnormal ANS testing, which demonstrated both sympathetic and parasympathetic defects, i.e., generalized ANS dysfunction. Treatment with fludrocortisone effectively reversed the OH in four of the five patients. The OH was transient in these four patients. We believe it is important to recognize that OH may be the result of generalized ANS dysfunction in HIV-positive patients and that it can be effectively treated. 