When mice were placed in a novel environment, they exhibited behavioral activation, characterized by a high frequency of jumps, rearings, groomings, digging, etc. Naloxone exerted a dose-dependent antagonism of this behavior. The antagonism was stereospecific, with the enantiomer, (+)-naloxone failing to antagonize this behavior. Morphine-injected mice showed a different behavioral syndrome, i.e., Straub tail and a compulsive, robot-like ambulation around the perimeter of the bin, with a total absence of jumps, rearings, etc. The morphine behavioral syndrome was antagonized by naloxone at 1 mg/kg, while higher naloxone doses were required to antagonize the behavioral activation in a novel environment. These results suggest that stereospecific antagonism by naloxone is a necessary but not sufficient condition for defining opiate-like action.