In the present study we have reinvestigated the subtype of alpha 2-adrenoceptors expressed in human adipocytes (from subcutaneous and internal fat deposits) by means of radioligand binding using subtype-selective antagonists, and RNase mapping using a set of specific probes prepared from human alpha 2-adrenoceptors genes (alpha 2C2, alpha 2C4 and alpha 2C10). Comparison of the pharmacological properties of the human adipocyte alpha 2-adrenoceptors with those of the different human adrenoceptors expressed in COS-7 cells demonstrated that: i) human adipocyte alpha 2-adrenoceptors displays a KD for [3H]RX821002 and [3H]MK912 identical to that found in COS-7 cells transfected with the alpha 2C10 gene; ii) yohimbine and oxymetazoline is 1,000-fold more potent than prazosin to inhibit [3H]antagonist binding. RNase protection assays on cellular RNA prepared from the three fat deposits showed the presence of substantial amounts of alpha 2C10 transcripts: in contrast, mRNAs from alpha 2C2 and alpha 2C4 genes were undetectable. Altogether these results definitively establish that human adipocytes express only one alpha 2-adrenoceptor which is of the alpha 2A-subtype and encoded by the alpha 2C10 gene.