1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has been shown to modulate the immune function of monocytes and macrophages. Patients with end-stage renal disease (ESRD) on chronic hemodialysis treatment usually present a deficiency of this active form of vitamin D3. The aim of this study was to investigate the effect of 1,25(OH)2D3 replacement therapy on phagocytosis, bactericidal capacity, and oxidative metabolism of peripheral blood polymorphonuclear leukocytes (PMNL) and monocytes (MN) in chronic hemodialysis patients. Phagocyte function tests were performed before and after four weeks of an oral replacement therapy with 0.5 micrograms/day of 1,25(OH)2D3 (Rocaltrol). The superoxide (O2-) generation of monocytes, measured by cytochrome c reduction and lucigenin-enhanced chemiluminescence (CL) from patients receiving hemodialysis treatment was significantly diminished compared to healthy controls. After the replacement therapy with 1,25(OH)2D3 the O2- production showed a significant improvement, resulting in an increased cytochrome c reduction and lucigenin-CL response. The bactericidal capacity of MN was also impaired and exhibited a significant enhancement of their killing activity after the administration of 1,25(OH)2D3. On the other hand, the luminol-enhanced CL, which reflects the myeloperoxidase-dependent oxidative metabolism, and the phagocytic ability of MN was not affected by the hormone. The function of polymorphonuclear leukocytes (PMNL) from hemodialysis patients showed no impairment in the state of 1,25(OH)2D3 deficiency and the replacement of the hormone did not enhance their function. These results suggest that the deficiency of 1,25(OH)2D3 in patients with ESRD on chronic hemodialysis treatment may be responsible for an impaired monocyte function, which could be improved by an in vivo replacement of the hormone.