Calcium absorption is thought to occur only if calcium is in a soluble or dissociated form, although experimental evidence is lacking. The intestinal absorption of calcium oxalate, a small, neutral and virtually insoluble calcium salt, was elucidated in the whole body of awake rats. Suspensions of Ca-45 ascorbate, C-14-oxalic acid and doubly labeled Ca-45-[C-14]-oxalate were given by gavage to separate groups of rats. Following dosing, blood samples were drawn for up to 240 min through a previously inserted intravenous catheter. Serum was assayed for radioactive tracers, and data were then plotted as fraction of dose over time. Calcium absorption was 15% [with a loading of 0.3 mmol (15 mg) calcium], oxalic acid absorption was 22% and Ca-oxalate absorption was <2%. Appearance of Ca-45 from calcium ascorbate and C-14 from oxalic acid differed, whereas Ca-45 and C-14 from doubly labeled Ca-oxalate had identical serum appearance profiles. Therefore, we conclude that calcium oxalate was absorbed intact. Addition of excess, unlabeled calcium to the doubly-labeled calcium oxalate did not alter the relationship of the serum level of the two tracers, confirming absorption of calcium oxalate as the intact salt. Thus, calcium bound as a small, neutral, calcium salt such as calcium oxalate does not have to be dissociated prior to absorption. Possibly other small compounds would be similarly absorbed. These results alter our current understanding of calcium bioavailability from foods and therapeutic agents.