The 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) receptor mediates many of the actions of 1,25(OH)2D3 in cells of target tissues. Abnormalities in vitamin D receptor concentration and regulation exist in tissues of subjects with chronic renal failure and end-stage renal disease. There is evidence that inhibitors of vitamin D receptor-1,25(OH)2D3 binding and 1,25(OH)2D3 action are present in dialysates and sera of individuals with end-stage renal disease. The biological significance of decreased vitamin D receptor number and altered vitamin D receptor regulation in uraemia is unclear at present as responses to 1,25(OH)2D3 in uraemia have not been systematically compared with responses in normal subjects.