Coadministration of olanzapine, an atypical neuroleptic, with sulpiride, a selective D2 antagonist, is suggested as an efficient strategy for treating patients with resistant unremitting schizophrenia. The psychopharmacologic rationale that may account for the enhanced clinical efficacy of combining sulpiride with olanzapine and vice versa is the difference in affinity of the two drugs to brain receptors. Olanzapine affinity is related more to serotonin 5-HT2 than to dopamine-2, whereas sulpiride is considered a selective D2 blocker. The adjunction of a selective D2 antagonist to olanzapine may act as the olanzapine's augmentor by enhancing D2 blockage. This mode of treatment was introduced to six patients with chronic schizophrenia who showed noteworthy and rapid clinical improvement, supported by a decrease in their scores on the Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale. No bothersome side effects were noticed. This clinical approach is in accordance with the findings of previous reports assessing the efficacy of the combined treatment of clozapine and sulpiride. The grounds for this treatment regimen using olanzapine rather than clozapine are discussed, calling for further studies to affirm the hypothesis and clinical results.