Abstract. The aim of the present study was to investigate whether or not activation of imidazoline receptors modulates noradrenaline release in the rat isolated kidney. Kidneys were pre-exposed to 3H-noradrenaline and the renal nerves were stimulated with 6 pulses at 100Hz. The stimulation induced (S-I) outflow of radioactivity was taken as an index of endogenous noradrenaline release. The imidazoline derivatives clonidine (11000nmol/l) and moxonidine (101000nmol/l) inhibited S-I outflow of radioactivity with an EC50 of 6.8nmol/l and 62.5nmol/l and a maximum of 88% and 97%, respectively. The concentration response curves for clonidine and moxonidine were shifted to the right by the selective 2-adrenoceptor antagonist rauwolscine (0.1mol/l) in a parallel manner with identical pKBs of 8.52 and 8.46, respectively. Furthermore, the -adrenoceptor agonist ()--methylnoradrenaline (0.130nmol/l), which has no affinity for imidazoline binding sites, inhibited S-I outflow of radioactivity with an EC50 of 2.4nmol/l and a maximum of 94%. Rauwolscine (0.1mol/l) again shifted the concentration response curve for this -adrenoceptor agonist to the right with a pKB of 8.40. Moreover, the selective 2-adrenoceptor antagonist 2-[2-(2-methoxy-1,4-benzodioxanyl)]imidazoline HCl (RX821002, 0.01mol/l) shifted the concentration response curves for clonidine and moxonidine to the right with pKBs of 9.46 and 9.18, respectively. The 2-adrenoceptor antagonist 4-chloro-2-(2-imidazoline-2-ylamino)-isoindoline HCl (BDF6143, 11000nmol/l), which, in the presence of 2-adrenoceptor blockade, has been shown to inhibit noradrenaline release through activation of imidazoline receptors, inhibited S-I outflow of radioactivity with an EC50 of about 20.5nmol/l (with 1000nmol/l producing 60% inhibition). The inhibitory effects of BDF6143 and clonidine were abolished after pretreatment of the kidneys with the irreversible 2-adrenoceptor antagonist phenoxybenzamine (1mol/l). However, RX821002 did not alter and rauwolscine slightly antagonized the inhibitory effect of BDF6143. It is concluded that the imidazoline derivatives clonidine and moxonidine as well as the phenylethylamine ()--methylnoradrenaline inhibit noradrenaline release in rat isolated kidney exclusively through activation of prejunctional 2-adrenoceptors. BDF6143 inhibits noradrenaline release in rat isolated kidney through an 2-adrenoceptor-independent, possibly an imidazoline receptor mechanism.