To define the onset of the rise in intact parathyroid hormone (PTH) levels in renal insufficiency, we conducted a cross-sectional study of parameters of mineral metabolism in patients with varying degrees of renal impairment. Using an immunoradiometric assay to measure intact PTH levels, we found elevations in intact PTH levels as creatinine clearance approaches 60 ml/minute (serum creatinine near 1.8) and a significant inverse relationship between indices of renal function and intact PTH levels (r = -0.60, P < 0.001 for intact PTH and creatinine clearance.) Calcium and phosphate levels correlate less strongly with the degree of hyperparathyroidism (r = -0.39, P < 0.001 for total calcium; r = 0.31, P < 0.05 for phosphate). As a group, only patients with severe renal failure (creatinine clearance < 20 ml/minute) had 1,25-dihydroxyvitamin D levels below normal (11 +/- 4 [SEM] pg/dl, normal range 15-60). Intact and n-terminal PTH measurements correlate well in this patient population with varying degrees of renal insufficiency (r = 0.9, P < 0.001). Intact PTH can be elevated in patients with mild to moderate renal insufficiency, thus efforts to prevent the development of secondary hyperparathyroidism in renal failure should be undertaken early in the course of renal insufficiency.