The interactions of the opioid and adrenergic systems were investigated in the guinea pig myenteric plexus longitudinal muscle preparation. Morphine and azepexole (a highly selective α2-adrenergic agonist) inhibit the electrically induced contractions with ED50 of 1.9 × 10−7M and 3.1 × 10−6M, respectively. The effect of morphine but not that of azepexole was competitively antagonized by naloxone. Stimulation of the preparation at 10 Hz was used to induce endogenous opioid release that was unaffected by azepexole. The authors' findings indicate that the effects of morphine and azepexole are additive, but that there is no direct interaction between the opioid and adrenergic receptors in the ileum. These observations provide some additional insight into the ability of α2-agonists to enhance the effects of opioids and inhalation anesthetics.