The present study evaluates the role of 1,25(OH)2D in the pathogenesis of abnormal mineral metabolism in patients with early renal failure (ERF). This was accomplished by examining the calcemic response to PTH and the handling of an oral phosphate load both before and after 6 weeks of therapy with 1,25(OH)2D. Twelve patients with ERF and six normal volunteers were studied. Patients with ERF as compared with normal subjects have low serum phosphate, low urinary calcium, low serum 1,25(OH)2D, and high plasma PTH and urinary cyclic AMP (cAMP). With EDTA infusion, an impaired calcemic response to PTH is observed in patients with ERF. The phosphate load test shows that these patients have an increased ability to excrete phosphate. After 1,25(OH)2D therapy a significant increase in serum phosphate, urinary calcium, and a decrease in urinary cAMP is observed only in ERF patients. In addition, the impaired calcemic response to PTH improves significantly, the renal handling of phosphate becomes normal, and the low baseline level of 1,25(OH)2D increases to normal. A significant correlation between levels of 1,25(OH)2D and creatinine clearance is observed in both patients and normals. In summary, the present data suggest that a mild deficiency of 1,25(OH)2D is present in ERF patients. The pathophysiological consequence of such a deficiency in patients with ERF may be important.