The beta adrenergic receptors mediate the effects of endogenous catecholamines, such as epinephrine, by coupling to Gs to stimulate cAMP. Whereas 1 and β2 are found predominantly in heart, the β3 receptor is found primarily in adipose tissue. Activation of adipose β3 results in lipolysis and thermogenesis. A polymorphism in the human gene for β3 is associated with weight gain in obese patients (Clement et al., 1995). In addition, mice lacking the β3-adrenoceptor display increased total body fat, particularly on a high fat diet (Revelli et al., 1997). These observations indicate that 3 is a possible target for obesity treatments. β3 adrenoceptor membrane preparations are crude membrane preparations made from our proprietary stable recombinant cell lines to ensure high-level of GPCR surface expression; thus, they are ideal HTS tools for screening of antagonists of β3 adrenoceptor interactions. The membrane preparations exhibit a Kd of 0.69 nM for [125I]-(-) Iodocyanopindolol (ICYP). With 10 mg/well β3 Adrenoceptor Membrane Prep and 0.75 nM [125I]-(-)ICYP, a greater than 8-fold signal-to-background ratio was obtained.