Plasma homovanillic acid (pHVA) was measured over a 13 hr-period in 16 DMS-III-R schizophrenic patients, all treated with neuroleptic drugs and in a stable clinical and therapeutic status for the preceeding 12 months. Patients were categorized into deficit (n = 9) and nondeficit (n = 7) forms of schizophrenia according to the Schedule for the Deficit Syndrome (SDS) criteria. As compared to the nondeficit group, deficit patients display significantly lower mean pHVA concentrations from 9 AM to 12 AM and a lack of diurnal variations. None of the demographic, clinical, and therapeutic variables can explain these biological differences. These data suggest a specific biochemical basis for the deficit syndrome of schizophrenia as defined by the SDS criteria, that is, primary, enduring, negative symptoms.