Bone biopsies were performed and serum concentrations of vitamin D metabolites were measured in twenty-four patients with chronic renal failure. The concentrations of three metabolites--25-dihydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D (24,25-OH2D) and 1,25-dihydroxyvitamin D (1,25-OH2D)--were significantly lower in uraemic than in normal sera. There was a positive correlation between serum 24,25-OH2D and serum 25-OHD, whereas serum 1,25-OH2D values, which were independent of those of the other vitamin D metabolites, were negatively correlated with serum creatinine and serum inorganic phosphate. The two major skeletal lesions, osteomalacia and parathyroid osteopathy, while coexisting in many patients, varied independently in relation to their severity and were correlated with different vitamin D metabolites. The severity of osteomalacia was negatively correlated with the serum concentrations of 25-OHD and 24,25-OH2D while th severity of parathyroid osteopathy was negatively correlated with serum 1,25-OH2D values. To our knowledge these are the first systematic studies correlating skeletal histology with dihydroxylated vitamin D metabolites in renal failure in man.