The type of opioid receptors in the spinal cord involved in antinociception induced by cold water swimming (CWS) was studied in male ICR mice. Mice were submitted to CWS for 3 min and antinociception was measured 7 min after the CWS by the tail-flick test. Intrathecal (i.t.) injection of naltrindole (NTI, 5 micrograms) which blocked i.t. DPDPE ([D-Pen2,D-Pen5]en-kephalin, 5 micrograms)-induced antinociception, blocked the CWS-induced antinociception. On the other hand, i.t. injection of CTOP (D-Phe-Cys-Try-D-Try-Orn-Thr-Pen-Thr-NH2, 50 ng) and norbinaltorphimine (nor-BNI, 5 micrograms) which blocked i.t. DAMGO ([D-Ala2,NHPhe4,Gly-ol]enkephalin, 10 ng)- and U50,488H (trans(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzeneacetamide, 75 micrograms)-induced antinociception, respectively, did not block CWS-induced antinociception. Intrathecal pretreatment with antisense oligodeoxynucleotide to delta-opioid receptor mRNA (delta-AS oligo, 163 pmol) once a day for 1 to 3 days caused a time-dependent attenuation of CWS-induced antinociception. delta-AS at doses from 1.6 to 163 pmol pretreated i.t. for 3 days caused a dose-dependent blockade of CWS-induced antinociception. However, i.t. pretreatment with mismatch oligodeoxynucleotide (MM oligo, 163 pmol) for 3 days did not affect the CWS-induced antinociception. The results indicate that CWS-induced antinociception is mediated by the stimulation of delta-opioid receptors in the spinal cord.