Poor neuroleptic response is a major unresolved clinical problem. Precise data concerning the frequency of poor neuroleptic response are not available. The implementation of treatment modalities that are specifically recommended for non-responders (such as clozapine) increases the desirability of such data. This study evaluated the proportion of acutely exacerbated schizophrenics who remained unimproved by consecutive administration of haloperidol, chlorpromazine and perphenazine, in randomly determined order. The overall improvement rate was 95%. The frequency of good responses to the first, second and third drug were 67%, 55%, and 67% respectively. Differences in receptor affinity profile might explain the added beneficial effect of a second or third drug.