There exists considerable evidence implicating the alpha (alpha) adrenergic system in the superior therapeutic effects of clozapine for the treatment of schizophrenia, as also its associated adverse hypersalivation side effect. It would seem plausible for variants of the adrenoceptors to be associated with the clozapine response. The present study tested the hypothesis that a biallelic polymorphism in the promoter region of the alpha2a-adrenoceptor gene confers susceptibility to schizophrenia, and is associated with a clozapine-induced (favorable) therapeutic response and/or a clozapine-induced hypersalivation. Ninety-seven treatment-resistant schizophrenic patients were assessed using the Brief Psychiatric Rating Scale before and after clozapine treatment. The results of clozapine treatment demonstrated that the alpha2a-adrenoceptor gene variants did not play a major role in the susceptibility, hypersalivation adverse effect or clozapine response of patients with schizophrenia. The polymorphism of the alpha2a-adrenoceptor gene investigated is not likely to play a major role in the pathogenesis of schizophrenic disorders or clozapine response, although the hypothesis that these genes are implicated in the cognitive deficit and polydipsia associated with schizophrenic disorders may, however, still warrant further study.