Gastrointestinal blood loss due to aspirin can be minimized by administering the drug as a dilute solution of acetylsalicylate. Bleeding can be prevented in normal subjects by adding sufficiently large amounts of antacids to the solution. These concepts have been applied to the formulation of very rapidly dissolving, highly buffered aspirin tablets. Daily oral administration of 2.6 gm of aspirin for seven days to 15 normal adult volunteers resulted in an average daily blood loss of 2.3 ml (in excess of the 0.4 ml control value) when a nationally distributed brand of aspirin tablets was used. An experimental tablet preparation caused only 0.7 ml daily blood loss, a reduction of 69%. Similar results were obtained with highly buffered chewable tablets. There was an inverse rank-order correlation between buffer capacity and blood loss in the series of tablet preparations tested.