Recently, it has been shown that intrathecal injection of norepinephrine and the mixed A₁/A₂ adenosine agonist5′-N-ethylcar☐amide adenosine (NECA) interact in a supra-additive manner to produce antinociception. The present studies were designed to determined whetherα₁orα₂ noradrenergic receptors are involved in producing the antinociception induced by NECA and norepinephrine. The results indicated that intrathecal injection of NECA (0.97–4.9 nmol), theα₂ noradrenertic agonist clonidine (3.8–375 nmol), or theα₁ agonist phenylephrine (4.9–73.4 nmol) produced dose-dependent antinociception in rats. Furthermore, intrathecal injection of subeffective doses of NECA and clonidine interacted supra-additively to produce potent antinociception. In contrast, no supra-additive interaction was observed between NECA and phenylephrine. The supra-additive interaction of NECA and clonidine did not appear to result from alteractions in cardiovascular tone because changes in blood pressure and nociceptive thresholds were not correlated in time. These results suggests that the noradrenergic component of the supra-additive interaction between adenosine A₂ receptor agonists and noradrenergic agonists is mediated byα₂ noradrenergic receptors.