Isolated perfused rat adrenal glands were prelabeled with 3H-norepinephrine and catecholamine secretion was evoked by nerve stimulation (10 Hz, supramaximal voltage for 30 seconds) or acetylcholine (ACh)(5.4 micrograms) injection. Nerve stimulation evoked significant increases in tritium (16371 +/- 2109 cpm) and catecholamine (11.5 +/- 1.0 ng norepinephrine [NE], 123.1 +/- 13.0 ng epinephrine [EP]) release from the adrenal medulla. ACh injection evoked catecholamine release, but failed to increase tritium release. In the presence of etorphine, the nerve stimulation-mediated release of tritium, NE and EP was inhibited. In contrast, the ACh-mediated release of NE but not EP was inhibited by etorphine. In a previous publication (1), we have shown that 3H-NE is taken up by sympathetic nerve endings contained in extra adrenal tissue removed along with the adrenal gland during the surgery, but not by chromaffin cells. Therefore, the inhibitory effect of etorphine on NE, EP and tritium release evoked by nerve stimulation suggests a functional role for opiate receptors on transmitter release from sympathetic and splanchnic nerve endings. However, the differential effect of etorphine on NE and EP release evoked by ACh injection indicates that opiate receptors on chromaffin cells modulates NE but not EP release.