In this double-blind six-week study, 98 chronic schizophrenic patients receiving long-term neuroleptic treatment and trihexyphenidyl were switched to either placebo or study trihexyphenidyl. Fifty-one (68%) of the 75 patients given placebo versus 1 of the 23 patients who continued on active trihexyphenidyl developed severe worsening of extrapyramidal signs, necessitating early termination from the study. Twenty-one (28%) of the placebo patients versus 2 (8.7%) of the trihexyphenidyl patients developed less severe worsening. Furthermore, 50 (66.6%) of the placebo patients but only 2 (8.7%) of the trihexyphenidyl patients had psychotic or other severe physical symptoms related to withdrawal of prestudy antiparkinsonian medication. The authors conclude that these data support the need for continuous use of antiparkinsonian medication in the long-term neuroleptic therapy of chronic schizophrenic patients.