The study was designed to investigate the role of nitric oxide (NO) in the diabetes-induced decrease of the antinociceptive effect of morphine. The nociceptive threshold in diabetic and non-diabetic mice was measured in the tail-flick test. Streptozotocin (200 mg/kg i.p.) was administered to induce experimental diabetes in the mice. Four weeks after the administration of streptozotocin, the tail-flick test was performed and urinary nitrite concentration was estimated using Greiss reagent. Experimental diabetes markedly decreased the antinociceptive effect of morphine (10 microg in 5 microl/mice i.c.v.) and significantly increased the urinary nitrite concentration. Administration of aminoguanidine (12 mg/mice) markedly improved the antinociceptive effect of morphine and attenuated the increase in urinary nitrite concentration in diabetic mice. It may be tentatively concluded that an increase in NO formation may be responsible for the observed decrease in antinociceptive effect of morphine in diabetic mice.