The formaldehyde method was used to examine the interaction of PGE1 with morphine, beta-endorphin and Met-enkephalin on rat mast cells by their effects on IgE-mediated 14C-serotonin release. PGE1 (2x10(-8) -2x10(-5) M) caused a dose-related inhibition of the mediator release 1 min after an antigen challenge, and morphine (3x10(-7) -3x10(-5) M) reversed this PGE1 effect dose-dependently and stereospecifically; naloxone (2x10(-4) M) antagonized this action of morphine. Beta-Endorphin (3x10(-7) -10(-5) M) and Met-enkephalin (3x10(-6) -10(-4) M) mimicked this morphine action dose-dependently and were antagonized by naloxone (2x10(-4) M). These results suggest that morphine and endorphins modulate immunological mediator release from rat mast cells through opioid receptors.