Background - Despite a new generation of antipsychotics, many patients with schizophrenia achieve only partial syndromal remission. In an effort to improve symptomatic and functional outcomes, it has become common practice to combine antipsychotic medications. Since this strategy is largely unproven and expensive, empirical trials are urgently needed. Our group has found in an open trial that adding risperidone to clozapine was well tolerated and led to improvement in psychopathology. Additional support for increasing D2 blockade in clozapine partial responders comes form two small studies using sulpiride and pimozide. We hypothesize that there is a subgroup of patients who might benefit from additional D2 blockade beyond what clozapine alone accomplishes.