The majority of chronic hemodialysis patients have elevated serum iPTH levels and bone disease characterized by osteitis fibrosa. However, a small group of patients develop osteomalacic bone disease associated with normal or slightly elevated iPTH values and a tendency to hypercalcemia which occurs either spontaneously or after treatment with small doses of vitamin D sterols. To examine the causes of the relatively low iPTH levels, we evaluated the change in serum iPTH levels that occurred in response to acute hypocalcemia, produced by dialysis using a low calcium dialysate, in 11 patients with osteomalacia and 8 control hemodialysis patients. Dialysis against a dialysate free of calcium for 60 to 90 min led to a fall in serum calcium to 7.5 +/- 0.2 and 7.2 +/- 0.2 mg/dl in the osteomalacic and control patients, respectively. Serum iPTH rose in controls from 1380 +/- 287 to 1960 +/- 287 pg/ml (P less than 0.01), whereas in patients with osteomalacia it rose from 360 +/- 58 to 507 +/- 104 pg/ml (P less than 0.05), a value only slightly above normal for this PTH assay. These data suggest that the relatively low basal levels of serum iPTH do not arise as a consequence of physiologic suppression of parathyroid gland function. This reduction in parathyroid function could contribute to the pathogenesis of low turnover osteomalacia.