1. The influence of a chronic treatment with the delta-selective opioid antagonist naltrindole (1 mg kg-1) during the preweanling period (daily injections from birth to postnatal day 19), on the antinociceptive and sympatholytic effects of the alpha2-adrenergic agonist clonidine in male and female rats of 20 and 25 days of age was investigated. 2. Nociception was assessed using the tail immersion test (water at 50 degrees C) and plasma levels of adrenaline were measured by high-performance liquid chromatography. 3. The dose of clonidine (1.5 mg kg-1) and the time point at which nociceptive responses were recorded (30 min after the administration of the drug) were chosen on the basis of dose-response (0.5, 1, 1.5 and 2 mg kg-1) and time-response (5, 10, 15, 30 and 60 min) curves which were previously carried out in naive control neonatal rats. 4. In females, the functional blockade of the delta-receptor by neonatal naltrindole treatment did not modify the sympatholytic effect of clonidine but prevented clonidine induced antinociception. Conversely, in males naltrindole treatment allowed the appearance of clonidine antinociception and the sympatholytic effect of clonidine. 5. The results indicate that the delta-receptor is involved in the modulation of antinociceptive and sympatholytic responses to clonidine in neonatal rats and suggest the existence of sex differences in the interactions between delta-opioid and alpha2-adrenergic receptors.