Patients with idiopathic hypercalciuria (IH) have decreased renal calcium reabsorption, most marked in the post-prandial state, but mechanisms are unknown. We compared 29 subjects with IH and 17 normal subjects (N) each fed identical meals. Urine and blood samples were collected fasting and after meals. Levels of 3 candidate signallers - serum calcium (Sca), insulin (I), and plasma parathyroid hormone (PTH) did not differ between IH and N either fasting or fed, but all changed with feeding, and the change in Sca was greater in IH than in N. Regression analysis of fractional excretion of calcium (FECa) was significant for PTH and Sca in IH but not N. Using multivariable analysis, Sca entered the model while PTH and I did not. To avoid internal correlation we decomposed FECa into its independent terms: adjusted urine calcium (UCa) and UFCa molarity. Analyses using adjusted Uca and unadjusted Uca parallel those using FECa, showing a dominant effect of Sca with no effect of PTH or I. The effect of Sca may be mediated via VDR-stimulated increased abundance of CaSR, which is supported by the fact PTH levels also seem more responsive to serum Ca in IH than in N. Although our data support an effect of Sca on FECa and urine Ca which is more marked in IH than in N, it can account for only a modest fraction of the meal effect, perhaps 10 - 20%, suggesting additional mediators are also responsible for the exaggerated post-prandial hypercalciuria seen in IH.