The aim of this study was to determine whether or not mast cells store or bind morphine. Injection of a potent mast cell depleter, compound 48/80 to dogs, 10 minutes after completion of a perfusion of 30 mg/kg of morphine produced a large concomitant increase of both morphine and histamine in blood samples drawn from the aorta. This increase is transient and statistically significant up to 1 minute following the injection of the drug. Morphine and histamine levels decrease rapidly as they reach the general circulation and are subjected to distribution. Injection of compound 48/80 one hour after the end of the morphine perfusion produces a less prominent increase in morphine and histamine levels. In both instances, subsequent doses of compound 48/80 failed to produce any increase in the levels of morphine or histamine. All these findings strongly indicate that in these dogs, the increase in morphine levels following 48/80 injection is caused by a release of morphine, bound or stored in the mast cells of the lungs, during the course of the perfusion.