The specific binding of the dopamine antagonist 3H-spiperone to lymphocytes from a healthy control group (n = 40), a group of acute, unmedicated schizophrenic patients (n = 27), and a psychiatric control group (n = 16) was investigated. There were no differences in binding parameters between the healthy controls (Bmax 2.6 +/- 0.7 fmoles/10(6) cells; Kd 0.17 +/- 0.07 nM) and the psychiatric control group. Binding capacity of 3H-spiperone was significantly increased in lymphocytes from the schizophrenic patients (Bmax 14.4 +/- 9.3 fmoles/10(6) cells). Moreover, a slight decrease in affinity was observed (Kd 0.44 +/- 0.21 nM). Because the increase in binding appeared only in schizophrenic patients, this peripheral model could prove valuable as a diagnostic criterion.