Abstract Warm water swimming produces in mice an opiate-like antinociceptive response. Chronic swimming produces tolerance to the antinociceptive response and, depending on the schedule, cross-tolerance with morphine and naloxone intensified withdrawal signs. Low affinity [ 3H]Leu-enkephalin binding to brain homogenates at low temperature was significantly reduced in acutely swum mice and chronically swum mice whether or not they were swum. Preincubation at 37°C abolished all between-group differences. Results following chronic swimming were similar whether or not the schedule produced morphine cross-tolerance. These results were discussed in terms of the interpretation that reduced binding reflects increased in vivo occupation of opioid binding sites.