The binding parameters for the dopamine antagonist 3H-spiperone to lymphocytes were investigated in nonmedicated schizophrenics (N = 43), in medicated schizophrenics (N = 25), as well as in 38 first- and second-degree relatives of schizophrenics, in a psychiatric control group (N = 27) and in normal, healthy controls (N = 40). The density of lymphocyte 3H-spiperone binding sites (Bmax) was significantly increased in all acute and chronic schizophrenic patients and in patients undergoing neuroleptic treatment for 2 weeks to several months and remained on a constant level during a drug-free remission period, suggesting that Bmax is a state independent variable. Elevated binding seems to be associated with schizophrenia; it could not be found in other psychiatric patients. In pedigree and family studies it became obvious that all relatives with one or more previous episodes of schizophrenia had similar increased binding capacity. But even in some well-state relatives elevated spiperone binding could be found, although they never had symptoms of the disease. Among these relatives of schizophrenics, there was an association between increased spiperone binding and the transmission of the disease. Although conclusive data about the precise genetic control obtainable in twin studies are still missing, we would suggest that elevated lymphocyte spiperone binding may be a marker of susceptibility to schizophrenia.