Dopamine D2 receptors were solubilized from synaptosomal membranes of the bovine caudate nucleus using a novel zwitterionic detergent 3-[(3-deoxycholamidopropyl)-dimethylammonio]-1-propane sulfonate (DCHAPS) supplemented with 1,2-propylene glycol. Optimal conditions for solubilization were: 0.12% DCHAPS, 5% 1,2-propylene glycol, 8 mg/ml membrane protein, 30 min, 4 degrees and the yield of the D2 receptors was 36.1%. The soluble extract retained the ability to bind [3H]spiperone. This binding was of high affinity (Kd = 2.28 +/- 0.16 nM), reversible and saturable (Bmax = 1.68 +/- 0.06 pmol/mg protein). The order of potencies of dopamine agonists and antagonists for inhibition of binding, paralleled that observed on membrane-bound D2 receptors (correlation factor r = 0.96). The stereo-specificity of solubilized receptors toward the pairs (+)-[(-)butaclamol, cis(Z)-]trans(E)flupenthixol and dihydroergosine/dihydroergosinine was pronounced.