Renal osteodystrophy is a debilitating complication of chronic renal failure and secondary hyperparathyroidism (2HPTH) is one of its central features. 2HPTH develops as a result of the low levels of serum calcium and 1,25-dihydroxyvitamin D [1,25(OH)2D3] and the high serum phosphate that occur in chronic renal failure. 1,25(OH)2D3 markedly decreases PTH gene transcription and its lack leads to 2HPTH. A low serum calcium increases PTH mRNA and iPTH levels while a high serum calcium has no effect on PTH gene expression. In experimental uremia there are increased levels of PTH mRNA. In chronic renal failure there is a shift in the calcium set-point to the right. This may be a function of a change in properties of the parathyroid cell calcium receptor, which is a G-protein coupled calcium sensor.