Whole-body $gamma$-irradiation(WBI), which produces an oxidative stress, is reported to attenuate the acute antinociceptive action of morphine (a $mu$-opioid receptor agonist), but not DPLPE (a $delta$-opioid receptor agonist), in mice. Recently, we also reported that antinociceptive effect of morphine, but not $eta$-endorphin (a novel $varepsilon$-opioid receptor agonist), was attenuated by oxidative stress. These findings prompted us to investigate the effect of WBI on the antinociception of morphine and $eta$-endorphin in mice. Mice were exposed to WBI (5 Gy) from a $^{60}Co$ gamma-source and tested 2 hours later for antinociception produced by intracerebroventricular administration of morphine or $eta$-endorphin using the hot water tail-immersion and the writhing tests. WBI significantly attenuated the antinociception produced by morphine only in the hot water tail-immersion test, whereas the antinociception of $eta$-endorphin was significantly potentiated by WBI in both tests. These results demonstrate a differential sensitivity of $mu$- and $varepsilon$-opioid receptors to WBI, and support the hypothesis that morphine and $eta$-endorphin administered supraspinally produce antinociception by different neuronal mechanisms.