Background: Changes in serum parathyroid hormone (PTH) within minutes are known only to be mediated by changes in ionized calcium. Recent animal studies show ingestion of a low phosphorus meal can lower serum PTH within 15 min, before changes in serum ionized calcium or phosphorus occur, suggesting a rapid gastrointestinal signal may regulate PTH. Methods: Eight hemodialysis patients with secondary hyperparathyroidism were admitted twice to a metabolic unit and ate a high and low phosphorus meal after an overnight fast. Serum PTH, total and ionized calcium, phosphorus, pH, and glucose were measured at 0, 15, 30, 60, 120 and 240 min. In the second protocol, we examined the possible role of volume or glucose changes in rapid PTH suppression by administering intravenous saline and glucose after an overnight fast to 6 patients, with similar testing. Results: Intact PTH decreased 24% from 419 ± 331 at baseline to 312 ± 221 pg/ml (p = 0.002) 15 min after a meal. Total and ionized calcium and pH did not change, glucose rose by 15 min, and phosphorus changed only after 60–90 min. During the second protocol, saline and glucose infusions failed to change PTH. Conclusions: In dialysis patients, a glucose-containing meal, with or without phosphorus, rapidly suppresses serum PTH ∼25% within 15 min. This effect is not mediated by changes in ionized calcium, phosphorus, pH, glucose, or insulin. These data suggest there may be an as yet unknown enteral signal that rapidly suppresses PTH.