Opioid receptors have been pharmacologically classified as ${mu}$, ${delta}$, ${kappa}$ and ${varepsilon}$. We have recently reported that the antinociceptive effect of morphine (a ${mu}$-opioid receptor agonist), but not that of ${eta}$-endorphin (a novel ${mu}/{varepsilon}$-opioid receptor agonist), is attenuated by whole body irradiation (WBI). It is unclear at present whether WBI has differential effects on the antinociceptive effects of ${mu}-$, ${delta}-$, ${kappa}-$ and ${varepsilon}$-opioid receptor agonists. In our current experiments, male ICR mice were exposed to WBI (5Gy) from a $^{60}Co$ gamma-source and the antinociceptive effects of opioid receptor agonists were assessed two hours later using the hot water ($52^{circ}C$) tail-immersion test. Morphine and $D-Ala^2$, $N-Me-Phe^4$, Gly-olenkephalin (DAMGO), [$D-Pen^2-D-Pen^5$] enkephalin (DPDPE), trans-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide (U50,488H), and ${eta}$-endorphin were tested as agonists for ${mu}$, ${delta}$, ${kappa}$, and ${varepsilon}$-opioid receptors, respectively. WBI significantly attenuated the antinociceptive effects of morphine and DAMGO, but increased those of ${eta}$-endorphin. The antinociceptive effects of DPDPE and U50,488H were not affected by WBI. In addition, to more preciously understand the differential effects of WBI on ${mu}-$ and ${varepsilon}$-opioid receptor agonists, we assessed pretreatment effects of ${eta}$-funaltrexamine (${eta}$-FNA, a ${mu}$-opioid receptor antagonist) or ${eta}$-$endorphin_{1-27}$ (${eta}$-$EP_{1-27}$, an ${varepsilon}$-opioid receptor antagonist), and found that pretreatment with ${eta}$-FNA significantly attenuated the antinociceptive effects of morphine and ${eta}$-endorphin by WBI. ${eta}$-$EP_{1-27}$ significantly reversed the attenuation of morphine by WBI and significantly attenuated the increased effects of ${eta}$-endorphin by WBI. The results demonstrate differential sensitivities of opioid receptors to WBI, especially for ${mu}-$ and ${varepsilon}$-opioid receptors.