Fifteen volunteers each received two of six aspirin solutions in a balanced incomplete block design. The solutions contained 0, 3, 6, 10, 16, and 34 mEq of sodium bicarbonate-citric acid buffer and 650 mg of aspirin. Plasma aspirin levels were measured in blood samples collected frequently during the first 2.5 h, and the accumulation of aspirin, salicylic acid, and salicyluric acid were measured over 2 and 24 h. The most rapid absorption rates occurred with solutions which contained small quantities of the antacid buffer. The 3- and 6-mEq antacid buffers had mean maximal aspirin concentrations of 17.3 and 17.8 micrograms/mL, respectively. In the absence of the buffering agent, the 650 mg of aspirin failed to dissolve completely and gave a mean maximal plasma concentration of 13.4 micrograms/mL. With 34 mEq of a buffering agent, a delay in the onset of absorption occurred and the presystemic hydrolysis increased. This was probably because more aspirin was emptied into and absorbed from the small intestine with higher concentrations of the buffering agent.