Background/Aims: Elevated concentration of plasma homocysteine (tHcy) is common in renal patients, however, the reason behind the resistance to vitamin B<sub>12</sub> and folate therapy are poorly understood. Methods: We investigated vitamin B<sub>12</sub> uptake by mononuclear cells (MC) from predialysis patients (n = 19) as compared to healthy controls (n = 15). Serum levels of tHcy, methylmalonic acid and cystathionine, holotranscobalamin (holoTC), total vitamin B<sub>12</sub> and folate were also measured. Results: The uptake of vitamin B<sub>12</sub> by MC from renal patients was lower than that by MC from controls (9.3 vs. 12.5 pg/3 × 10<sup>6</sup> cells; p = 0.001). Nonetheless, the receptor-binding capacity was comparable between patients and controls (6.1 vs. 6.5 pg/3 × 10<sup>6</sup> cells; p = 0.627). Average reduction of vitamin B<sub>12</sub> uptake in patients as compared to the controls was 18.1%. Conclusions: Our results show that vitamin B<sub>12</sub> uptake is impaired in MC from renal patients, with no evidence that the surface receptor is down-regulated. High serum concentrations of holoTC are common in renal patients and might be related to a generalized resistance to this vitamin. Serum concentrations of vitamin B<sub>12</sub> within the reference range are not likely to ensure vitamin delivery into the cells. Supraphysiological doses of vitamin B<sub>12</sub> may be necessary to deliver a sufficient amount of the vitamins to the cells via mechanisms largely independent of holoTC receptor.