Cyclosporine (CsA), an immunosuppressant, is used widely to prevent rejection of transplanted organs. It is extensively metabolized in the liver by hydroxylation and demethylation. Since phenytoin is used extensively post-transplant as an anti-convulsant, we studied the effect of chronic treatment with phenytoin on CsA by determining the disposition of CsA, prior to and after chronic treatment with phenytoin (30 mg/kg, po) for 5 days. CsA was analyzed by HPLC. The clearance (CL) of CsA was significantly enhanced following treatment with phenytoin when compared to the CL values obtained pretreatment (15.46 +/- 0.76 vs. 25.3 +/- 3.11 ml/min/kg). There were no significant changes in the volume of distribution of CsA. From the above data, we conclude that phenytoin probably induces the metabolism of CsA.