Intracerebroventricular (i.c.v.) injection of the delta-opioid receptor antagonist naltrindole hydrochloride (2.2-22.2 nmol) in mice produced a dose-dependent increase in tail flick and hot plate latencies with respective ED50 and 95% confidence limits of 10.6 (8.3-13.9) and 16.4 (9.2-62.3) nmol. This increase in response latencies was antagonized by 1 mg/kg s.c. naloxone or by i.c.v. coadministration of 1.4 nmol ICI-174,864, a selective peptidergic delta-receptor antagonist. Pretreatment 24 h earlier with the irreversible mu-receptor antagonist beta-funaltrexamine (6 nmol i.c.v.) or 1 h earlier with the selective kappa-receptor antagonist nor-binaltorphimine (100 nmol i.c.v.) did not attenuate the antinociceptive effects of naltrindole. These data indicate that high doses of naltrindole may have agonist activity at supraspinal delta-opioid receptors in the mouse.