In this prospective controlled study the purpose was to assess the long-term safety of calcium-free dialysate (O Ca) for hemodialysis and to determine the optimum calcium replacement. With this technique there is no calcium in the dialysate and calcium is infused into the drip chamber distal to the dialyzer. We compared the use of a standard bicarbonate dialysate with a calcium free dialysate in two groups of patients. One group (study 1) received 10 mmol/hour Ca replacement, the other (study 2) received 13.3 mmol/hour Ca during dialysis. Each O Ca period lasted six months. This experimental period was compared with the six months preceding and following in the same patient and as well, with a concurrent control group who received standard bicarbonate dialysis either with 1.5 mmol/l calcium in the dialysate in study 1 or 1.75 mmol/l in study 2. Each group had nine to eleven subjects. No adverse effects were seen in either of the studies. With 10 mmol/hour calcium replacement there was a small but not significant rise in the pre-dialysis intact parathyroid hormone level (PTH) whereas in all the other groups it remained the same or fell. There was significantly less rise in the post-dialysis calcium in the same group and this was associated with a small but not significant fall in both pre-dialysis total and ionized calcium. It was concluded that the O Ca technique can be used for long periods and that 13.3 mmol/hour is a satisfactory replacement using Discap 140 dialyzers or their equivalent.