The experiments served to characterize the receptors mediating the inhibitory effect of alpha-adrenergic drugs on K+ (20 mM)-induced [3H]noradrenaline (NA) and [3H]5-hydroxytryptamine ([3H]5-HT) release from slices of the dorsal part of rat hippocampus. Dose-response curves were constructed using the cumulative dose-response technique (Frankhuyzen and Mulder, 1981). All of the adrenergic agonist drugs examined inhibited the K+-induced [3H]NA release. NA appeared to have the highest intrinsic activity followed by adrenaline. Clonidine and adrenaline had similar intrinsic activities, while that of oxymetazoline was lowest. The highest pD2 values were observed for oxymetazoline and clonidine, being slightly higher than that of adrenaline followed by NA. By far the lowest pD2 values was observed for phenylephrine. With the exception of phenylephrine, all of the agonists also inhibited the K+-induced [3H]5-HT release. NA, adrenaline and oxymetazoline appeared to have similar intrinsic activities, while that of clonidine was considerably lower. The pD2 values of NA and adrenaline were not significantly different but were somewhat lower than those of oxymetazoline and clonidine. Similar antagonistic effects of phentolamine and yohimbine were observed with respect to the adrenergic inhibition of K+-induced [3H]NA and [3H]5-HT release. Prazosin, however, appeared to be ineffective in both instances. It is concluded from these results that the presynaptic adrenergic inhibiton of [3H]NA as well as [3H]5-HT release is mediated by alpha 2-adrenoceptors located on noradrenergic and serotonergic varicosities, respectively. Furthermore, our data suggest that these alpha 2-adrenoceptors are not pharmacologically identical.