Di-isopropyl phosphofluoridate (DFP, 0.1--1.5 mg/kg, s.c.) produced antinociception in rats as measured by the hot plate test. Naloxone reduced DFP-induced antinociception but did not affect the attenuated locomotor activity or hypothermia produced by DFP. Animals rendered tolerant to the antinociceptive action of morphine failed to exhibit cross tolerance to the antinociceptive action of DFP. Morphine- and DFP-induced antinociceptive states were antagonized by MR 2266 and GPA 1843, the (-)-isomers of 5,9 alpha-Diethyl-2-(3-furylmethyl)-2'-hydroxy-6, 7-benzomorphan and -2-allyl-2'-hydroxy-9 beta-methyl-5-phenyl-6, 7-benzomorphan hydrochloride, respectively; the corresponding (+)-isomers, MR 2267 and GPA 1847, did not antagonize the antinociceptive state produced by DFP or morphine. These results suggest that DFP-induced antinociception may be mediated via the release of endogenous opioids; however, this could occur at sites different from those concerned with morphine tolerance.