Apatite and brushite kidney stones share calcium and phosphate as their main inorganic components. We tested the hypothesis that these stone types differ in the amount of proteins present in the stones. Intact stones were intensively analyzed by microcomputed tomography (micro CT) for both morphology (including the volume of voids, i.e., space devoid of X-ray dense material) and mineral type. To extract all proteins present in kidney stones in soluble form we developed a three-step extraction procedure using the ground stone powder. Apatite stones had significantly higher levels of total protein content and void volume compared to brushite stones. The void volume was highly correlated with the total protein contents in all stones (r2 = 0.61, P < 0.0001), and brushite stones contained significantly fewer void regions and proteins than did apatite stones (3.2 +/- 4.5% voids for brushite vs. 10.8 +/- 11.2% for apatite, P < 0.005; 4.1 +/- 1.6% protein for brushite vs. 6.0 +/- 2.4% for apatite, P < 0.03). Morphological observations other than void volume did not correlate with protein content of stones, and neither did the presence or absence of minor mineral components. Our results show that protein content of brushite and apatite stones is higher than that was previously thought, and also suggest that micro CT-visible void regions are related to the presence of protein.