Tissue calcium content from 246 diagnostic human renal biopsies was measured to assess whether elevated tissue calcium concentration could be demonstrated to exist early during the course of human renal disease or was only a manifestation of advanced renal impairment. Renal calcium content correlated significantly with serum creatinine (r = +0.23, P less than 0.001, N = 246); serum phosphate P less than 0.001, N = 169) but not with serum calcium (r = -0.10, P greater than 0.1, N = 193). Fivefold greater calcium content was measured in biopsied patients with normal renal function than in normal postmortem renal tissue (35.7 +/- 5.2 vs. 7.6 +/- 0.7 mgCa/100 g wet renal tissue, P less than 0.001). Those biopsied patients with significant functional impairment (SCr greater than 1.5 mg/dl) had a higher mean level of serum phosphorus and serum [Ca] X [P] product than patients with normal renal function (5.19 +/- 0.22 vs. 3.92 +/- 0.11 mg P/dl and 44.8 +/- 1.8 vs. 35.7 +/- 1.2 mg2/dl2, respectively), and slightly higher renal calcium content (85.3 +/- 32.2 vs. 35.7 +/- 5.2 Ca/100 g wet renal tissue, P = 0.06), which correlated with histologic calcium deposition (r = +0.52, P less than 0.02, N = 20). These findings are consistent with the hypothesis that renal calcium deposition begins early in the course of a variety of renal diseases and hence may play a secondary pathogenetic role that accelerates progression to chronic renal failure. Severity of renal calcium deposition is equally closely related to hyperphosphatemia and to the level of renal impairment.