1. Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) and is being developed for the prevention of rejection following solid organ transplantation. This crossover study investigated the effect of food and antacid (Maalox TC) on the plasma pharmacokinetics of MPA and its inactive glucuronide metabolite MPAG after giving single 2 g MMF doses orally to rheumatoid arthritis patients. 2. With food, the AUC of MPA in plasma was equivalent to that following an overnight fast. MPA tmax was slightly delayed and Cmax was lowered about 25%, consistent with delay in gastric emptying in the fed state. MPAG Cmax and AUC were higher in the fed relative to the fasting state, suggesting more complex processes involving changes in glucuronidation may also be occurring with food. 3. With antacid, AUC of MPA was lowered about 15% compared with fasting and Cmax was decreased 37%. Plasma MPAG parameters were similarly reduced. These parallel changes in MPA and MPAG are consistent with reduced absorption. 4. The changes in MPA with both food and antacid are small in comparison with the interpatient variability and are not likely to have clinically major effects; the changes in MPAG are of mechanistic interest.