In order to determine the species which would provide the highest yield of soluble and specific D2-type dopamine receptors, the striata from human, calf and canine brains were solubilized by 1% digitonin. The receptors were detected with [3H]spiperone, using Sephadex G-50 columns or polyethylene glycol precipitation. The soluble D2-sites from the human and canine tissue had about the same KD and rank order of drug affinities as the native membrane preparations. The binding characteristics of the calf D2-receptors were considerably altered, however, upon solubilization; the affinities for spiperone and chloropromazine were reduced 12-fold, and the non-specific binding increased from 28 to 50%. Calf caudate is a poor choice for dopamine receptor solubilization using digitonin. The solubilized canine tissue, however, provided an excellent source of D2-receptors because of its similarity to soluble human D2-receptors and its stability in solution.