The antinociceptive effects of various i.v. doses (2.5, 3.75, 5, 10, 15 and 20 mg/kg) of a prodrug mixed inhibitor of enkephalin degrading enzymes, PC 12, were tested in normal and Freund's adjuvant-induced arthritic rats, using vocalization thresholds to paw pressure as a nociceptive test. In normal animals, PC 12 produced a dose-dependent antinociceptive effect over the 2.5-15 mg/kg range, but the time-course of the response was shorter with the dose of 20 mg/kg. In arthritic rats, PC 12 had no significant effect at 2.5 mg/kg, but induced a highly significant dose-dependent antinociceptive action with 3.5 and 5 mg/kg, which decreased with the highest doses. The antinociceptive effect of PC 12 (10 mg/kg i.v.) was prevented by naloxone (0.5 mg/kg i.v.) in the two categories of rats, providing evidence for the involvement of opioid receptors. These results are discussed in relation with the increased level of endogenous opioid substances in the spinal dorsal horn of arthritic rats and the nociceptive test used.