Both calcium-containing and non calcium-containing phosphate binders can increase gastrointestinal calcium absorption. Previously, we observed that lanthanum carbonate administration to rats with renal failure is not associated with an increased calciuria. Additionally, lanthanum carbonate treatment in dialysis patients has been associated with a less pronounced initial decrease in serum PTH compared to other phosphate binders. For 8 days, male Wistar rats received a diet supplemented with 2% lanthanum carbonate, 2% sevelamer, 2% calcium carbonate or 2% cellulose. Calciuria was found to be increased in animals treated with sevelamer or calcium carbonate, but not with lanthanum carbonate. In animals with renal failure, cumulative calcium excretion showed similar results. Serum ionized calcium levels were increased after 2 days of treatment with sevelamer, while calcium carbonate showed a smaller increase. Lanthanum carbonate did not induce differences. In animals with renal failure, no differences were found between the sevelamer, calcium carbonate and control groups. Lanthanum carbonate, however, induced lower ionized calcium levels within 2 days of treatment. These results were confirmed in normal human volunteers, showing lower net calcium absorption after a single dose of lanthanum carbonate, compared to sevelamer carbonate. In conclusion, these two non calcium-containing phosphate binding agents showed a differential effect on gastrointestinal calcium absorption. These findings may help to improve management of calcium balance in patients with renal failure, including concomitant use of vitamin D.