• Alprazolam was added, under double-blind conditions, to stable fluphenazine hydrochloride regimens in 12 symptomatic, chronically ill inpatients with schizophrenia. The addition of alprazolam was associated with significant, albeit modest, reductions in global psychosis, thought disorder, and paranoia ratings, with a return to pretreatment levels on discontinuation of alprazolam treatment. Improvement in "negative symptoms" such as emotional withdrawal paralleled the changes in "positive symptoms" but did not, in itself, reach statistical significance. There were no significant changes in group mean plasma levels of homovanillic acid or 3-methoxy-4-hydroxyphenylglycol during alprazolam treatment, although group mean serum cortisol levels were significantly decreased by alprazolam treatment. Patients who responded favorably to alprazolam treatment were significantly more psychotic or anxious before treatment, were older, showed significant alprazolam-associated reductions in plasma levels of homovanillic acid, and had significantly more prominent prefrontal cortex atrophy on computed tomographic scans than patients in whom alprazolam was without therapeutic effect. These preliminary data, based on a small sample, suggest that some patients with schizophrenia who are only partially responsive to standard neuroleptic treatment may benefit from the addition of triazolobenzodiazepines, such as alprazolam.