The effects of decreasing serum levels of PTH after parathyroidectomy on circulating levels of 1 alpha,25-dihydroxyvitamin D [1,25-(OH)2D] and bone Gla protein (BGP) were studied in seven patients treated with chronic maintenance dialysis. Before surgery, all patients had extremely elevated levels of PTH, low normal or low levels of 1,25-(OH)2D, high levels of BGP, and histological signs of excess PTH action on bone. The fall in PTH levels after surgery resulted in a further decline in 1,25-(OH)2D concentrations and a reduction in circulating BGP levels. This fall in serum 1,25-(OH)2D and BGP levels was not related to serum calcium or phosphorus. Administration of 1,25-(OH)2D3 from 4-6 months after surgery did not significantly affect serum levels of BGP or PTH. These data indicate that 1,25-(OH)2D is still under regulatory control of PTH in patients without excretory kidney function. This might reflect some remaining endocrine activity of the kidneys in these dialyzed patients or extrarenal production of 1,25-(OH)2D. In addition, the data show that serum BGP levels in renal failure are elevated due not only to impaired clearance but also to PTH-mediated acceleration in bone turnover. Therapy with 1,25-(OH)2D3 in these patients resulted in supraphysiological serum 1,25-(OH)2D levels which did not stimulate BGP production.