Injection of naloxone to morphine perfused naive dogs caused a transient increase in the blood level of morphine although no concomitant increase in the blood level of histamine was observed. The increase in the blood level of morphine following naloxone administration was statistically significant (p<0.001) within the 1st min and decreased rapidly to control values by 10 min. A second injection of naloxone administered 2 h later did not increase the blood level of morphine. Similarly, administration of naloxone to morphine perfused dogs pretreated with compound 48/80, a potent mast cell depleter, revealed no increase in the blood level of morphine. These findings indicate that morphine was promptly bound to the mast cells after perfusion and the origin of morphine released into the blood by naloxone was the mast cells.