We studied 21 dialysis patients who became hypercalcemic without vitamin D or calcium therapy and compared them to 28 dialysis patients who were not hypercalcemic. In the hypercalcemic group, the mean ionized-calcium level was elevated compared to normal subjects (5.4 ± 0.4 vs. 4.9 ± 0.1; p < 0.001), while the ionized-calcium level in the control dialysis patients was below normal (4.5 ± 0.4 vs. 4.9 ± 0.1; p < 0.001). Bone biopsies were performed in all patients. Two thirds of the hypercalcemic patients had low-turnover osteodystrophy (LTO, predominantly osteomalacia), a fraction significantly higher than in the control dialysis patients (13/21 vs. 8/28, respectively; p < 0.05). The hypercalcemic patients with LTO had markedly elevated surface bone aluminum (63 ± 24% of all trabecular surfaces). In contrast, the nonhypercalcemic dialysis patients with LTO and all patients with osteitis fibrosa had minimal surface bone aluminum. Hypercalcemic patients with osteitis fibrosa had a significantly lower mean N-terminal parathyroid hormone (PTH) value than did nonhypercalcemic patients with osteitis fibrosa (149 ± 81 vs. 278 ± 135 pg/ml, respectively; p < 0.005). Both mean values were markedly elevated in comparison with those obtained in normal subjects (16 ± 5 pg/ml). In contrast, patients with LTO, irrespective of the calcium level, had mean PTH values that were not significantly different from those of normal subjects. A PTH level greater than 100 pg/ml was 95% sensitive and 87% specific for osteitis fibrosa, as demonstrated by histomorphometry in nonhypercalcemic dialysis patients. However, this level was only 62% sensitive and 77% specific for a diagnosis of osteitis fibrosa in hypercalcemic dialysis patients. The hypercalcemic patients had an increased mortality at 1 year of follow-up compared to control dialysis patients, after controlling for the difference in age. Mortality at 1 year was 38% in those hypercalcemic patients who were more than 50 years of age. The majority of the deaths occurred in hypercalcemic patients with aluminum-related bone disease. In addition, this group of patients had the greatest disability.In summary, we found that hypercalcemic patients had increased disability and mortality and that aluminum-related bone disease was more common in this group of patients than was osteitis fibrosa. The N-terminal PTH level was not helpful in the differential diagnosis of the type of bone disease present in those patients who were hyperc