Components of grapefruit juice have been shown to inhibit CYP3A4 activity, the enzyme involved in cyclosporine metabolism. Eleven medically stable patients (seven males, four females) receiving cyclosporine following kidney transplantation were instructed to take their usual dose of cyclosporine with water for 1 week (Phase 1), with grapefruit juice (8 ounces) for 1 week (Phase 2) and again with water for 1 week (Phase 3). Trough blood samples were obtained at the end of each phase for measurement of cyclosporine concentration using a specific monoclonal whole blood radioimmunoassay. Cyclosporine trough concentrations averaged 116.9 +/- 51.6 ng ml(-1) in the first phase, 145.3 +/- 44.7 ng ml(-1) with grapefruit juice (P < 0.05 compared with the first and third phases) and 111.2 +/- 56.1 ng ml(-1) in the third phase. Cyclosporine concentrations increased in 8 of 11 patients when given with grapefruit juice (mean increase 32%; range -4 to 97%) and declined in 10 of 11 when subjects resumed taking cyclosporine with water (mean decrease 27%). These results suggest that grapefruit juice increases trough concentrations of cyclosporine in blood, possibly by inhibiting pre-hepatic gut wall metabolism, and could be useful in optimizing therapy with this drug.