1. There is an ongoing discussion regarding the elevated binding of 3 H-spiperone to lymphocytes of schizophrenic patients. Several authors described an atypical binding pattern with a saturable high-affinity and a nonsaturable binding site both displaceable by (+)-butaclamol. Recent findings are still controversial, possibly due to methodological differences. The authors investigated 3 H-spiperone binding to different peripheral blood cells including B- and T-lymphoblastoids.2. B-lymphocytes (K D = 0.081 nM; B m a x = 0.46 x 10 - 1 5 mol/ 10 6 cells) and macrophages (K D = 0.11 nM, B m a x = 2.44 x 10 - 1 5 mol/ 10 6 cells) are characterized by a minor but saturable binding of 3 H-spiperone in a concentration range between 0.5 and 1 nM. Above 1 nM, only non-saturable binding was measurable. Interestingly, Epstein-Barr virus (EBV) transformed lymphoblastoids (K D = 0.13 nM) have nearly the same affinity for 3 H-spiperone as native B-cells, but an increased number of binding sites (B m a x = 1.76 x 10 - 1 5 mol/ 10 6 cells).3. Membranes from B-lymphoblastoids displayed a saturable binding in a concentration between 0 and 1.8 nM of 3 H-spiperone (K D = 0.5 nM and B m a x = 1.72 x 10 - 1 5 mol/ mg protein). Extraction with 1 % digitonin resulted in a similar binding characteristic (K D = 0.17 nM and B m a x = 1.97 x 10 - 1 5 mol/ mg protein).4. T-cells, granulocytes and MOLT-3-cells did not show a saturable binding even not at high concentrations of 3 H-spiperone.5. The pharmacological profile of the high-affinity 3 H-spiperone binding site is clearly different from the dopamine D 2 and D 4 , serotonin 5-HT 2 histamine H 1 and noradrenergic alpha 1 and alpha 2 receptor, respectively.6. In summary, the results suggest that spiperone binding studies to enriched lymphocytes of psychiatric patients should be interpreted cautiously. Variable amounts of leucocytes might result in a higher proportion of nonsaturable, butaclamol displaceable spiperone binding with relevance for the calculation of K D and B m a x of the saturable high-affinity site. Interestingly, homogenous B-lymphoblastoid cell lines have the same binding characteristics as native B-lymphocytes and therefore should be recommended for characterization of 3 H-spiperone binding sites.