Effects of the anticholinergic drugs trihexyphenidyl and biperiden on plasma concentrations of bromperidol and its reduced metabolite were studied. Subjects comprised 20 schizophrenic inpatients taking bromperidol, 6-18 mg/ day for 1-9 weeks. Patients were randomly allocated to one of two treatment sequences: trihexyphenidyl-biperiden (n = 12) or biperiden-trihexyphenidyl (n = 8). Each sequence consisted of two 2-week phases, with no washout period between the two phases. The daily dose of trihexyphenidyl was 8 mg and that of biperiden 6 mg. Plasma concentrations of bromperidol and reduced bromperidol were measured using high-performance liquid chromatography (HPLC). There was no significant difference in plasma bromperidol or reduced bromperidol concentrations among baseline, trihexyphenidyl and biperiden phases: 7.3 +/- 3.7 versus 7.2 +/- 4.1 versus 7.0 +/- 4.3 ng/ml and 2.0 +/- 2.1 versus 2.2 +/- 2.1 versus 1.9 +/- 2.0 ng/ml, respectively. The present study thus suggests that neither trihexyphenidyl nor biperiden affects plasma concentrations of bromperidol and its reduced metabolite.