The present investigations examined possible interdependence among serotonergic, noradrenergic and adenosinergic pathways as spinal antinociceptive systems. ED50 values for antinociception induced by intrathecal injections of noradrenergic, serotonergic or adenosinergic agonists in mice were determined. These results were compared to ED50 values determined when an antagonist or a sub-antinociceptive dose of a second agonist was coadministered i.t. with agonists. Interactions observed when serotonergic and adenosinergic agents were coadministered suggest that antinociception induced by serotonin (i.t.) is mediated, in part, via serotonin-stimulated release of adenosine. The mechanism by which norepinephrine administered i.t. induced antinociception, however, appeared to be independent of serotonergic and adenosinergic pathways.