Calcium channel blockers (CCB) are considered the agents of choice to treat hypertension in cyclosporine (CsA)-treated renal transplant patients. Verapamil, diltiazem, and nicardipine, but not nifedipine or isradipine, can significantly increase CsA levels. The effect of a new CCB, amlodipine, has not been established. However, some hospitals are routinely switching patients to amlodipine from other CCB for reasons of cost. A case of a man with stable CsA levels who developed significantly increased CsA levels after being changed to amlodipine is presented along with a prospective trial to formally examine this issue. Eleven hypertensive, CsA-treated renal transplant patients were placed on amlodipine for an average of 6.9 wk and later withdrawn. Three measurements of CsA trough level, blood pressure, serum creatinine concentration, and BUN were obtained at baseline, during treatment with amlodipine, and after withdrawal of amlodipine. CsA levels on amlodipine increased an average of 40% above baseline (P = 0.003) and decreased to baseline (P = 0.001) after amlodipine was withdrawn, despite no significant change in CsA dose. Additionally, there was no change in serum creatinine, BUN, or mean arterial pressure values. Amlodipine can increase CsA levels by an average of 40% in hypertensive renal transplant patients, despite a stable CsA dose. This important effect must be considered when initiating or discontinuing amlodipine or when substituting amlodipine for other CCB.