The presence of functional dopamine receptors on differentiated cells of the mammalian immune system is still under discussion. This study has utilized (-)-[3H]sulpiride as a ligand, to detect the presence of recognition sites of the dopamine D2 receptor family on human T- and B-lymphocytes. The (-)-[3H]sulpiride binding was of high affinity (Kd 0.9 nM +/- 0.2 nM), specific, saturable (Bmax 10.2 +/- 1.4 fmol/10(6) cells) and reversible. The pharmacological characterization of the recognition site suggests similarities mainly with the D2 and D4 rather than D3 subtype of dopamine receptor. Furthermore, dopamine treatment was able to reduce the intracellular cAMP levels of lymphocytes stimulated with forskolin, thus suggesting a potential functional significance of this dopamine receptor in mediating neural-immune interactions.