Background. Moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Cyclosporine (CsA) has been suggested to interfere with folate-assisted remethylation of homocysteine, thus causing hyperhomocysteinemia. But, this issue is controversial. In this experimental study, we attempted to determine the association between CsA administration and total homocysteine levels. Working with rabbits that have normal creatinine levels, we obviated the misleading effects of renal functional variations, which are the most important confounding factors affecting total homocysteine level.