Since [3H]emonapride ([3H]YM-09151-2), a benzamide neuroleptic, consistently detects more dopamine D2 receptors than [3H]spiperone in the same tissue, we tested whether this property was inherent in the cloned dopamine D2 receptor. We found that the density of dopamine D2 receptors labelled by [3H]emonapride was 1.5-fold to 2-fold (mean of 1.8-fold) higher than the density of dopamine D2 receptors labelled by [3H]spiperone in cells expressing cloned dopamine D2 receptors (either the short form (from rat) or the long form (from human)), matching similar findings in anterior pituitary tissue (rat or pig) or in post-mortem human caudate nucleus tissue. The situation was similar for another benzamide, [3H]raclopride, which revealed 1.3-fold to 1.8-fold (mean of 1.5-fold) more binding sites than that for [3H]spiperone in cell membranes containing cloned dopamine D2 receptors. The apparently different dopamine D2 receptor densities revealed by these two types of 3H-ligands (i.e. [3H]spiperone and the [3H]benzamides), therefore, arise from an inherent property of the dopamine D2 receptor protein. These findings for the cloned dopamine D2 receptor, therefore, partly explain the higher dopamine D2 receptor density measured in human brain (by positron emission tomography) when using radioactive raclopride compared to results using radioactive methylspiperone.(ABSTRACT TRUNCATED AT 250 WORDS)