The experimental butyrophenone compound, trifluperidol, was compared with trifluoperazine and phenobarbital under double-blind conditions in a group of 60 hospitalized chronic schizophrenic patients. Therapeutic response was evaluated by means of 15 quantitative psychiatric, psychologic, and ward behavior measures. Both trifluperidol and trifluoperazine were clearly superior to phenobarbital, which failed to effect notable improvement in any of the 20 treated subjects. Trifluperidol had a greater and more rapid therapeutic effect than trifluoperazine as measured in the global ratings of improvement, and there was also suggestion in the psychologic data of greater improvement in immediate memory and greater reduction of symptoms reflecting chronicity and deterioration. The results of this study, as well as a review of three recent controlled comparative studies of trifluperidol, suggest that trifluperidol may well be the drug of choice for schizophrenic patients.