Cyclosporin A (CsA) is an important immunosuppressant that is prone to numerous drug interactions. Grapefruit juice has been investigated, as a possible adjunct to CsA dosing in adult renal transplant recipients, to decrease CsA metabolism and reduce dosages. This study investigated this combination in pediatric renal transplant patients. Six stable pediatric renal transplant patients were entered into an open-label, four-period cross-over study in which patients were given their current CsA dose as either an oral solution (CsA-Sol) or a microemulsion (CsA-ME). In addition, drugs were administered concurrently with water or grapefruit juice. Steady-state pharmacokinetic profiles were taken during each of the four periods. Following the concurrent administration of grapefruit juice, CsA whole-blood 12-h trough levels were significantly increased during CsA-Sol dosing. Furthermore, the CsA elimination rate constant was significantly reduced during the same period. After CsA-ME dosing, no differences in CsA pharmacokinetics were found between concurrent water or grapefruit ingestion. Grapefruit juice co-administration reduced the production of CsA metabolites, AM1 and AM9, during CsA-Sol dosing. No changes in CsA metabolite production were found when patients were given CsA-ME with grapefruit juice as compared with water. Hence, alterations in CsA absorption and elimination occur with concurrent grapefruit juice ingestion when stable pediatric renal transplant patients are taking the oral CsA solution, but not the microemulsion formulation. These changes may be mediated by alterations in intestinal or hepatic metabolism, or drug absorption. The effect of grapefruit juice on CsA absorption is not readily predictable in these patients.