Serum vitamin D metabolites and their relationship with dietary intake of phosphate were evaluated in 41 adult patients with early renal failure (glomerular filtration rate [GFR] 50 +/- 12 ml/min). On free diet, mean serum levels of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] were reduced and were a function of GFR and dietary intake of phosphate (beta-weight coefficients were 0.69 and -0.49, respectively). Serum levels of 24, 25(OH)2D3 were comparable to controls and were significantly correlated with serum 25(OH)D3 concentrations only. After 29 +/- 2 months of phosphate restricted (700 mg), calcium supplemented (1,300-1,800 mg) diet, serum phosphate and parathyroid hormone (PTH) levels were unchanged and serum calcium, 1,25(OH)2D3 and 24,25(OH)2D3 concentrations significantly increased in those patients whose GFR did not change. On the other hand, serum PTH increased and serum vitamin D metabolites remained persistently low in those patients whose GFR declined to 12 +/- 5 ml/min. A retrospective analysis of bone histology in 234 patients with chronic renal failure showed that in early renal failure (GFR 75-31 ml/min) the prevalence of osteomalacia and bone resorption was reduced by phosphate restriction (12 vs. 33%, p less than 0.05, and 12 vs. 28%, p = not significant, respectively). In advanced renal failure (GFR 30-10 ml/min), phosphate restriction reduced the prevalence of osteoclastic bone disease (17 vs. 61%, p less than 0.001), but did not change that of osteomalacia (35 vs. 32%, not significant).(ABSTRACT TRUNCATED AT 250 WORDS)