F344 and Lewis rats show different responses to opioids in several experimental paradigms. In this study we have used the specific A-opioid agonist DAMGO to find out if these differences could be attributed to heterogeneity of A-opioid receptors. The density of [H3]DAMGO binding sites was similar in the brain cortex and spinal cord of both strains, but DAMGO affinity for A-opioid receptors was higher in F344 tissues. Moreover, a parallel study of the effects of DAMGO on electrically-evoked twitches of isolated vasa deferentia revealed that this drug was also more effective in F344 preparations. These results suggest that A-opioid receptors of F344 rats are more sensitive to pharmacological stimulation in vitro, which could be related to a higher drug affinity. D 2003 Elsevier Science Inc. All rights reserved.