Calcium supplements are widely used for the treatment of osteoporosis. The bioavailability of these preparations is unknown. Because poor tablet dissolution accounts for a majority of drug bioavailability problems, we determined the in vitro dissolution at 30, 60, and 90 minutes of 27 commercially available calcium carbonate supplements using the method of the U.S. Pharmacopoiea. At 30 minutes, five preparations (18%) were more than 75% dissolved, four (15%) between 33 and 74%, and the remaining 18 (67%) were less than 33% dissolved. After 90 minutes, 17 (63%) of the preparations were less than 50% dissolved. Dissolution correlated negatively with the weight of filler (noncalcium carbonate material in the tablet) (rs = -0.51, P less than 0.01) but not with tablet hardness or cost. Similar to previous studies, we also found no correlation of dissolution with the stated calcium content, chemical source of calcium carbonate (oyster shell or chemical precipitate), or retail source. We conclude that there is a wide range of in vitro dissolution among the calcium carbonate preparations tested, and that the filler is an important determinant of the dissolution of these tablets. These results raise concern about the bioavailability of the calcium in these preparations and may have important implications for the therapeutic use of the various calcium carbonate supplements.