We assessed the effect of naloxonazine, a selective mu 1-opioid receptor antagonist, on antinociception produced by intrathecal or intracerebroventricular injections of morphine in streptozotocin-induced diabetic mice. The antinociceptive effect of morphine (10 micrograms), administered i.c.v., was significantly less in diabetic mice than in non-diabetic mice. The antinociceptive effect of i.c.v. morphine was significantly reduced in both diabetic and non-diabetic mice following pretreatment with naloxonazine. There were no significant differences in the antinociceptive effect of morphine (1 microgram, i.t.) in diabetic and non-diabetic mice. Furthermore, naloxonazine had no significant effect on the antinociceptive effect of i.t. morphine in either diabetic or non-diabetic mice. On the other hand, the antinociceptive effects of i.c.v. and i.t. morphine were significantly reduced following pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist, in both diabetic and non-diabetic mice. In conclusion, mice with diabetes are selectively hyporesponsive to supraspinal mu 1-opioid receptor-mediated antinociception, but are normally responsive to activation of spinal mu 2-opioid receptors.