Reports over the last 20 years suggest that pimozide, a neuroleptic of the diphenylbutylpiperidine (DPBP) group, might be helpful in the treatment of negative symptoms of schizophrenia, which are considered less responsive to standard neuroleptics than are positive symptoms. Research suggests that neuroleptic drugs of the DPBP group possess a unique property--potent calcium channel antagonism--which could explain their ability to relieve negative symptoms. Earlier reports, however, used measures not specifically designed to assess the negative syndrome. The Positive and Negative Syndrome Scale (PANSS) was developed and standardized to measure the negative syndrome in schizophrenia. The authors used the PANSS to study the effects of pimozide in a 6-week, open clinical trial with 10 neuroleptic-resistant schizophrenic inpatients who had prominent deficit features. Negative but not positive symptoms improved significantly, suggesting that the drug might target the negative profile. The authors discuss possible pharmacologic mechanisms for pimozide's potentially distinct clinical properties.