Idazoxan, a selective alpha 2-adrenergic antagonist, was added to stable doses of fluphenazine treatment in six patients with schizophrenia who participated in a double-blind, placebo-controlled pharmacologic study. Compared with fluphenazine alone, combining idazoxan (mean dose, 120 mg/day) with fluphenazine (mean dose, 28 mg/day) resulted in a significant decrease in Brief Psychiatric Rating Scale total symptoms (p < 0.05). Symptom ratings returned to baseline upon idazoxan discontinuation. No significant effects of idazoxan were observed on fluphenazine levels in plasma or on extrapyramidal symptoms. These pilot data are compatible with the notion that increased noradrenergic neurotransmission may enhance the therapeutic effects of typical neuroleptics in schizophrenia.