The effects of repeated ingestion of grapefruit juice, an inhibitor of cytochrome P4503A4 (CYP3A4), on the steady-state plasma concentrations of haloperidol and reduced haloperidol were examined. Twelve schizophrenic inpatients receiving haloperidol 12 mg/day, ingested grapefruit juice 600 ml/day for 7 days. Blood samples were collected before and during grapefruit juice coadministration and 1 week after its discontinuation together with an assessment of clinical status. Plasma drug concentrations were measured using high-performance liquid chromatography. Clinical status for each patient was assessed by the Brief Psychiatric Rating Scale (BPRS) and the UKU side-effect rating scale (UKU). Plasma concentrations of haloperidol and reduced haloperidol during grapefruit juice coadministration (9.0 +/- 3.0 and 2.6 +/- 1.4 ng/ml, respectively) were not significantly different from those before grapefruit juice coadministration (9.1 +/- 2.8 and 2.6 +/- 1.5 ng/ml) or those 1 week after its discontinuation (8.8 +/- 2.7 and 2.6 +/- 1.3 ng/ml). There was no change in the scores of BPRS or UKU during the study period. The present results shows that grapefruit juice does not affect the plasma concentrations of haloperidol and reduced haloperidol or clinical status in patients receiving haloperidol.