This study was undertaken to determine the subtype of prejunctional alpha2-autoreceptors in human blood vessels. Segments of gastric and ileocolic arteries were incubated with [3H]noradrenaline and subsequently perifused with modified Krebs-Henseleit solution containing cocaine (12 microM). Five periods of electrical stimulation (S1-S5) were applied (1 Hz, 1 ms, 50 V for 1 min). Concentration-response curves for the facilitatory effect of eight alpha-adrenoceptor antagonists [rauwolscine, 2-[2-(2-methoxy-1,4-benzodioxanyl)] imidazoline (RX821002), yohimbine, phentolamine, idazoxan, 2-(2',6'-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxan (WB4101), spiroxatrine and prazosin] were determined. All antagonists enhanced the stimulation-evoked overflow of tritium, indicating the existence of alpha2-autoreceptors. The EC30% values of the antagonists (concentrations that increased the evoked overflow of tritium by 30%) were taken as a measure of affinity to the autoreceptors. Correlations between the pEC30% values obtained in the present study and the pKi values of the same antagonists at cloned human alpha2A-, alpha2B-, alpha2C-adrenoceptors expressed in Chinese hamster lung cells and at alpha2D-adrenoceptors in the rat submaxillary gland or the bovine pineal gland showed that the alpha2-autoreceptors in the human gastric and ileocolic arteries resemble most closely the alpha2A-subtype.