Quaternary ammonium derivatives of narcotic antagonists are commonly used in determining sites of action of opiates in the central nervous system and the periphery because it is widely assumed that they do not readily cross the blood-brain barrier, in contrast to their relatively non-polar tertiary counterparts. However, these compounds possess several unique pharmacological properties which have not been taken into consideration in the design of numerous investigations. This article reviews the current state of knowledge concerning the pharmacology of the quaternary narcotic antagonists, examines their use in physiological and behavioral studies of action of opiates, and proposes guidelines for the design of experiments involving these compounds.